GeneBe

rs34261028

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003000.3(SDHB):​c.424-25_424-14delTTCTTCTTCTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000245 in 1,226,374 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

SDHB
NM_003000.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.02

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDHBNM_003000.3 linkc.424-25_424-14delTTCTTCTTCTTC intron_variant Intron 4 of 7 ENST00000375499.8 NP_002991.2 P21912
SDHBNM_001407361.1 linkc.370-25_370-14delTTCTTCTTCTTC intron_variant Intron 4 of 7 NP_001394290.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SDHBENST00000375499.8 linkc.424-25_424-14delTTCTTCTTCTTC intron_variant Intron 4 of 7 1 NM_003000.3 ENSP00000364649.3 P21912

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000245
AC:
3
AN:
1226374
Hom.:
0
AF XY:
0.00000482
AC XY:
3
AN XY:
622212
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28930
American (AMR)
AF:
0.00
AC:
0
AN:
44354
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24580
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38596
South Asian (SAS)
AF:
0.0000369
AC:
3
AN:
81250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52116
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5264
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
898732
Other (OTH)
AF:
0.00
AC:
0
AN:
52552
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.0

Splicing

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

Publications

Other links and lift over

dbSNP: rs34261028; hg19: chr1-17354373; API