rs17290760

Variant names:

• chr9-32556382-A-G
• rs17290760
• NM_002493.5:c.319-2438T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002493.5(NDUFB6):​c.319-2438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,318 control chromosomes in the GnomAD database, including 1,018 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 0.10 (1018 hom., cov: 33)
• Consequence: NDUFB6 NM_002493.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 6 publications found

Genes affected

NDUFB6 (HGNC:7701): (NADH:ubiquinone oxidoreductase subunit B6) 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. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jan 2011]

SMIM27 (HGNC:31420): (small integral membrane protein 27) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB6	NM_002493.5	c.319-2438T>C		intron_variant	Intron 3 of 3	ENST00000379847.8	NP_002484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB6	ENST00000379847.8	c.319-2438T>C		intron_variant	Intron 3 of 3	1	NM_002493.5	ENSP00000369176.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15609 AN: 152200 Hom.: 1018 Cov.: 33

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.102 AC: 15612 AN: 152318 Hom.: 1018 Cov.: 33 AF XY: 0.101 AC XY: 7487 AN XY: 74482

African (AFR) AF: 0.0318 AC: 1324 AN: 41574

American (AMR) AF: 0.0875 AC: 1339 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3472

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5194

South Asian (SAS) AF: 0.0665 AC: 321 AN: 4828

European-Finnish (FIN) AF: 0.135 AC: 1435 AN: 10614

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9903 AN: 68018

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.132 Hom.: 4577

Bravo AF: 0.0968

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.33
PhyloP100		-0.096
Mutation Taster		=100/0	polymorphism (auto)

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: rs17290760; hg19: chr9-32556380;