rs381575

Positions:

• chr5-53617061-A-C
• chr5-53617061-A-T

Variant summary

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

The NM_002495.4(NDUFS4):​c.177+13531A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,988 control chromosomes in the GnomAD database, including 13,975 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 (13975 hom., cov: 31)
• Consequence: NDUFS4 NM_002495.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

NDUFS4 (HGNC:7711): (NADH:ubiquinone oxidoreductase subunit S4) This gene encodes an nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, or NADH:ubiquinone oxidoreductase). Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS4	NM_002495.4	c.177+13531A>C		intron_variant		ENST00000296684.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS4	ENST00000296684.10	c.177+13531A>C		intron_variant		1	NM_002495.4	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63371 AN: 151870 Hom.: 13957 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.417 AC: 63423 AN: 151988 Hom.: 13975 Cov.: 31 AF XY: 0.417 AC XY: 30937 AN XY: 74276

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.410

Alfa AF: 0.358 Hom.: 13030

Bravo AF: 0.425

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.11
DANN	Benign	0.53

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: rs381575; hg19: chr5-52912891;