2-97648394-C-T

Variant names:

• chr2-97648394-C-T
• rs1800649
• NM_001862.3:c.*286C>T

Variant summary

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

The ENST00000258424.3(COX5B):​c.*286C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 326,622 control chromosomes in the GnomAD database, including 52,926 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 0.48 (21230 hom., cov: 32)
  • Exomes 𝑓: 0.58 (31696 hom.)
• Consequence: COX5B ENST00000258424.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 15 publications found

Genes affected

COX5B (HGNC:2269): (cytochrome c oxidase subunit 5B) Cytochrome C oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane. The complex consists of 13 mitochondrial- and nuclear-encoded subunits. The mitochondrially-encoded subunits perform the electron transfer and proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex. This gene encodes the nuclear-encoded subunit Vb of the human mitochondrial respiratory chain enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000258424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX5B	NM_001862.3	MANE Select	c.*286C>T		downstream_gene	N/A	NP_001853.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX5B	ENST00000258424.3	TSL:1 MANE Select	c.*286C>T		downstream_gene	N/A	ENSP00000258424.2
	COX5B	ENST00000464949.5	TSL:5	n.*203C>T		downstream_gene	N/A
	COX5B	ENST00000491989.1	TSL:3	n.*215C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73366 AN: 151950 Hom.: 21232 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.580 AC: 101249 AN: 174554 Hom.: 31696 Cov.: 2 AF XY: 0.571 AC XY: 50654 AN XY: 88780

African (AFR) AF: 0.204 AC: 951 AN: 4660

American (AMR) AF: 0.421 AC: 1774 AN: 4216

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 3049 AN: 6490

East Asian (EAS) AF: 0.253 AC: 3036 AN: 11980

South Asian (SAS) AF: 0.220 AC: 1849 AN: 8390

European-Finnish (FIN) AF: 0.737 AC: 8661 AN: 11758

Middle Eastern (MID) AF: 0.441 AC: 416 AN: 944

European-Non Finnish (NFE) AF: 0.656 AC: 75154 AN: 114502

Other (OTH) AF: 0.548 AC: 6359 AN: 11614

GnomAD4 genome AF: 0.482 AC: 73359 AN: 152068 Hom.: 21230 Cov.: 32 AF XY: 0.479 AC XY: 35569 AN XY: 74332

African (AFR) AF: 0.199 AC: 8231 AN: 41462

American (AMR) AF: 0.451 AC: 6893 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1564 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1374 AN: 5184

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4810

European-Finnish (FIN) AF: 0.737 AC: 7803 AN: 10584

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44650 AN: 67952

Other (OTH) AF: 0.487 AC: 1028 AN: 2112

Alfa AF: 0.586 Hom.: 14167

Bravo AF: 0.453

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.57
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1800649; hg19: chr2-98264857;