rs10887993

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003000.3(SDHB):​c.200+1015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,018 control chromosomes in the GnomAD database, including 15,126 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 15126 hom., cov: 32)

Consequence

SDHB
NM_003000.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDHBNM_003000.3 linkuse as main transcriptc.200+1015C>T intron_variant ENST00000375499.8
SDHBNM_001407361.1 linkuse as main transcriptc.200+1015C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDHBENST00000375499.8 linkuse as main transcriptc.200+1015C>T intron_variant 1 NM_003000.3 P1

Frequencies

GnomAD3 genomes
AF:
0.421
AC:
64001
AN:
151900
Hom.:
15124
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.198
Gnomad AMI
AF:
0.586
Gnomad AMR
AF:
0.456
Gnomad ASJ
AF:
0.460
Gnomad EAS
AF:
0.297
Gnomad SAS
AF:
0.448
Gnomad FIN
AF:
0.491
Gnomad MID
AF:
0.475
Gnomad NFE
AF:
0.541
Gnomad OTH
AF:
0.442
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.421
AC:
64003
AN:
152018
Hom.:
15126
Cov.:
32
AF XY:
0.418
AC XY:
31053
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.197
Gnomad4 AMR
AF:
0.456
Gnomad4 ASJ
AF:
0.460
Gnomad4 EAS
AF:
0.297
Gnomad4 SAS
AF:
0.449
Gnomad4 FIN
AF:
0.491
Gnomad4 NFE
AF:
0.541
Gnomad4 OTH
AF:
0.437
Alfa
AF:
0.495
Hom.:
5939
Bravo
AF:
0.410
Asia WGS
AF:
0.354
AC:
1232
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.66
DANN
Benign
0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10887993; hg19: chr1-17370241; API