rs11927983

Variant names:

• chr3-179623246-G-A
• rs11927983
• NM_002492.4:c.450-674G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ENSG00000288698 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NDUFB5	NM_002492.4	c.450-674G>A		intron_variant	Intron 5 of 5	ENST00000259037.8	NP_002483.1
NDUFB5	NM_001199957.2	c.294-674G>A		intron_variant	Intron 3 of 3		NP_001186886.1
NDUFB5	NM_001199958.2	c.343-674G>A		intron_variant	Intron 4 of 4		NP_001186887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB5	ENST00000259037.8	c.450-674G>A		intron_variant	Intron 5 of 5	1	NM_002492.4	ENSP00000259037.3
ENSG00000288698	ENST00000680408.1	n.*78+4725G>A		intron_variant	Intron 4 of 25			ENSP00000506198.1

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

African (AFR) AF: 0.0537 AC: 2231 AN: 41562

American (AMR) AF: 0.00516 AC: 79 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5188

South Asian (SAS) AF: 0.0385 AC: 186 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 68028

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00780 Hom.: 39

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
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11927983; hg19: chr3-179341034;