rs360726

Positions:

• chr11-112118869-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000532699.1(ENSG00000255292):​n.314+29858T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,024 control chromosomes in the GnomAD database, including 34,172 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 0.63 (34172 hom., cov: 31)
• Consequence: ENSG00000255292 ENST00000532699.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

Genes affected

ENSG00000255292 (HGNC:):

SDHD (HGNC:10683): (succinate dehydrogenase complex subunit D) This gene encodes a member of complex II of the respiratory chain, which is responsible for the oxidation of succinate. The encoded protein is one of two integral membrane proteins anchoring the complex to the matrix side of the mitochondrial inner membrane. Mutations in this gene are associated with the formation of tumors, including hereditary paraganglioma. Transmission of disease occurs almost exclusively through the paternal allele, suggesting that this locus may be maternally imprinted. There are pseudogenes for this gene on chromosomes 1, 2, 3, 7, and 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000255292	ENST00000532699.1	n.314+29858T>C		intron_variant		3		ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96413 AN: 151906 Hom.: 34183 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.634 AC: 96417 AN: 152024 Hom.: 34172 Cov.: 31 AF XY: 0.637 AC XY: 47358 AN XY: 74296

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.648

Alfa AF: 0.761 Hom.: 102643

Bravo AF: 0.607

Asia WGS AF: 0.626 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs360726; hg19: chr11-111989592; COSMIC: COSV73256785;