rs1022580

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003000.3(SDHB):c.201-36G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 1,503,420 control chromosomes in the GnomAD database, including 710,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 69693 hom., cov: 32)

Exomes 𝑓: 0.97 ( 640992 hom. )

Consequence

SDHB
NM_003000.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.294

Publications

15 publications found

Variant links:

Genes affected

SDHB (HGNC:10681): (succinate dehydrogenase complex iron sulfur subunit B) This tumor suppressor gene encodes the iron-sulfur protein subunit of the succinate dehydrogenase (SDH) enzyme complex which plays a critical role in mitochondria. The SDH enzyme complex is composed of four nuclear-encoded subunits. This enzyme complex converts succinate to fumarate which releases electrons as part of the citric acid cycle, and the enzyme complex additionally provides an attachment site for released electrons to be transferred to the oxidative phosphorylation pathway. The SDH enzyme complex plays a role in oxygen-related gene regulation through its conversion of succinate, which is an oxygen sensor that stabilizes the hypoxia-inducible factor 1 (HIF1) transcription factor. Sporadic and familial mutations in this gene result in paragangliomas, pheochromocytoma, and gastrointestinal stromal tumors, supporting a link between mitochondrial dysfunction and tumorigenesis. Mutations in this gene are also implicated in nuclear type 4 mitochondrial complex II deficiency. [provided by RefSeq, Jun 2022]

SDHB Gene-Disease associations (from GenCC):

Carney-Stratakis syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
gastrointestinal stromal tumor
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
pheochromocytoma
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
pheochromocytoma/paraganglioma syndrome 4
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
renal cell carcinoma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
mitochondrial complex 2 deficiency, nuclear type 4
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex II deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SDHB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-17033181-C-A is Benign according to our data. Variant chr1-17033181-C-A is described in ClinVar as Benign. ClinVar VariationId is 258889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHB	NM_003000.3 link	c.201-36G>T		intron_variant	Intron 2 of 7	ENST00000375499.8	NP_002991.2	P21912
SDHB	NM_001407361.1 link	c.201-36G>T		intron_variant	Intron 2 of 7		NP_001394290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHB	ENST00000375499.8 link	c.201-36G>T		intron_variant	Intron 2 of 7	1	NM_003000.3	ENSP00000364649.3		P21912

Frequencies

GnomAD3 genomes

AF:

0.956

AC:

145515

AN:

152160

Hom.:

69638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.910

Gnomad AMI

AF:

0.934

Gnomad AMR

AF:

0.971

Gnomad ASJ

AF:

0.953

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.991

Gnomad FIN

AF:

0.979

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.973

Gnomad OTH

AF:

0.950

GnomAD2 exomes

AF:

0.973

AC:

241645

AN:

248256

AF XY:

0.974

show subpopulations

Gnomad AFR exome

AF:

0.915

Gnomad AMR exome

AF:

0.982

Gnomad ASJ exome

AF:

0.954

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.978

Gnomad NFE exome

AF:

0.972

Gnomad OTH exome

AF:

0.971

GnomAD4 exome

AF:

0.974

AC:

1315992

AN:

1351142

Hom.:

640992

Cov.:

AF XY:

0.974

AC XY:

660815

AN XY:

678160

show subpopulations

African (AFR)

AF:

0.913

AC:

28424

AN:

31122

American (AMR)

AF:

0.981

AC:

43557

AN:

44390

Ashkenazi Jewish (ASJ)

AF:

0.954

AC:

24156

AN:

25312

East Asian (EAS)

AF:

0.987

AC:

38687

AN:

39182

South Asian (SAS)

AF:

0.988

AC:

82707

AN:

83708

European-Finnish (FIN)

AF:

0.979

AC:

52176

AN:

53316

Middle Eastern (MID)

AF:

0.963

AC:

5291

AN:

5494

European-Non Finnish (NFE)

AF:

0.974

AC:

985985

AN:

1011962

Other (OTH)

AF:

0.971

AC:

55009

AN:

56656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1719

3438

5157

6876

8595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18962

37924

56886

75848

94810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.956

AC:

145628

AN:

152278

Hom.:

69693

Cov.:

AF XY:

0.958

AC XY:

71307

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.910

AC:

37789

AN:

41540

American (AMR)

AF:

0.971

AC:

14849

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.953

AC:

3305

AN:

3468

East Asian (EAS)

AF:

0.995

AC:

5153

AN:

5178

South Asian (SAS)

AF:

0.991

AC:

4787

AN:

4830

European-Finnish (FIN)

AF:

0.979

AC:

10401

AN:

10624

Middle Eastern (MID)

AF:

0.969

AC:

285

AN:

294

European-Non Finnish (NFE)

AF:

0.973

AC:

66197

AN:

68020

Other (OTH)

AF:

0.951

AC:

2010

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

338

676

1015

1353

1691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.964

Hom.:

102923

Bravo

AF:

0.953

Asia WGS

AF:

0.986

AC:

3430

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 22, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pheochromocytoma/paraganglioma syndrome 4

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mitochondrial complex 2 deficiency, nuclear type 4

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pheochromocytoma

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gastrointestinal stromal tumor

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.39

(source)

DANN

Benign

0.65

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over