rs12762

Variant names:

• chr3-120602092-C-T
• rs12762
• ENST00000485064.1:c.*799C>T

Variant summary

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

The ENST00000485064.1(NDUFB4):​c.*799C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,501,210 control chromosomes in the GnomAD database, including 11,532 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 (973 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10559 hom.)
• Consequence: NDUFB4 ENST00000485064.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 5 publications found

Genes affected

NDUFB4 (HGNC:7699): (NADH:ubiquinone oxidoreductase subunit B4) This gene encodes a non-catalytic subunit of the multisubunit NADH:ubiquinone oxidoreductase, the first enzyme complex in the mitochondrial electron transport chain (complex I). Mammalian complex I is composed of 45 different subunits and transfers electrons from NADH to ubiquinone. [provided by RefSeq, Dec 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB4	NM_004547.6	c.328-116C>T		intron_variant	Intron 2 of 2	ENST00000184266.3	NP_004538.2
NDUFB4	NM_001168331.2	c.*799C>T		3_prime_UTR_variant	Exon 2 of 2		NP_001161803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB4	ENST00000184266.3	c.328-116C>T		intron_variant	Intron 2 of 2	1	NM_004547.6	ENSP00000184266.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15674 AN: 151984 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.121 AC: 163599 AN: 1349108 Hom.: 10559 Cov.: 32 AF XY: 0.122 AC XY: 81199 AN XY: 665422

African (AFR) AF: 0.0342 AC: 980 AN: 28624

American (AMR) AF: 0.0853 AC: 1986 AN: 23290

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 6284 AN: 22642

East Asian (EAS) AF: 0.0296 AC: 1031 AN: 34774

South Asian (SAS) AF: 0.121 AC: 8556 AN: 70460

European-Finnish (FIN) AF: 0.136 AC: 6147 AN: 45312

Middle Eastern (MID) AF: 0.175 AC: 835 AN: 4758

European-Non Finnish (NFE) AF: 0.123 AC: 130871 AN: 1063890

Other (OTH) AF: 0.125 AC: 6909 AN: 55358

GnomAD4 genome AF: 0.103 AC: 15670 AN: 152102 Hom.: 973 Cov.: 32 AF XY: 0.104 AC XY: 7729 AN XY: 74350

African (AFR) AF: 0.0405 AC: 1683 AN: 41508

American (AMR) AF: 0.105 AC: 1597 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 938 AN: 3466

East Asian (EAS) AF: 0.0398 AC: 206 AN: 5170

South Asian (SAS) AF: 0.111 AC: 535 AN: 4806

European-Finnish (FIN) AF: 0.137 AC: 1443 AN: 10566

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8815 AN: 67992

Other (OTH) AF: 0.130 AC: 275 AN: 2108

Alfa AF: 0.110 Hom.: 167

Bravo AF: 0.0961

Asia WGS AF: 0.0990 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.46
PhyloP100		0.033
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: rs12762; hg19: chr3-120320939; COSMIC: COSV109410496; COSMIC: COSV109410496;