rs11927983

Positions:

• chr3-179623246-G-A

Variant summary

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

The NM_002492.4(NDUFB5):​c.450-674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 152,328 control chromosomes in the GnomAD database, including 68 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 0.018 (68 hom., cov: 32)
• Consequence: NDUFB5 NM_002492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660

Genes affected

NDUFB5 (HGNC:7700): (NADH:ubiquinone oxidoreductase subunit B5) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). 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. Three 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB5	NM_002492.4	c.450-674G>A		intron_variant		ENST00000259037.8	NP_002483.1
NDUFB5	NM_001199957.2	c.294-674G>A		intron_variant			NP_001186886.1
NDUFB5	NM_001199958.2	c.343-674G>A		intron_variant			NP_001186887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB5	ENST00000259037.8	c.450-674G>A		intron_variant		1	NM_002492.4	ENSP00000259037	P1

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2729 AN: 152212 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.0180 AC: 2736 AN: 152328 Hom.: 68 Cov.: 32 AF XY: 0.0179 AC XY: 1332 AN XY: 74490

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.0385

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00585 Hom.: 24

Bravo AF: 0.0186

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.42

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: rs11927983; hg19: chr3-179341034;