2-206137835-A-T

Position:

• chr2-206137835-A-T

Variant summary

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

The NM_005006.7(NDUFS1):​c.1392+650T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,106 control chromosomes in the GnomAD database, including 22,379 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 0.53 (22379 hom., cov: 33)
• Consequence: NDUFS1 NM_005006.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

NDUFS1 (HGNC:7707): (NADH:ubiquinone oxidoreductase core subunit S1) The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS1	NM_005006.7	c.1392+650T>A		intron_variant		ENST00000233190.11	NP_004997.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS1	ENST00000233190.11	c.1392+650T>A		intron_variant		1	NM_005006.7	ENSP00000233190	P1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81229 AN: 151988 Hom.: 22347 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.535 AC: 81310 AN: 152106 Hom.: 22379 Cov.: 33 AF XY: 0.533 AC XY: 39600 AN XY: 74360

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.547

Alfa AF: 0.517 Hom.: 2596

Bravo AF: 0.537

Asia WGS AF: 0.331 AC: 1152 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.7
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs6435326; hg19: chr2-207002559;