15-74928627-C-T

Variant names:

• chr15-74928627-C-T
• rs11072513
• NM_004255.4:c.217+489G>A

Variant summary

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

The NM_004255.4(COX5A):​c.217+489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,146 control chromosomes in the GnomAD database, including 12,235 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 0.35 (12235 hom., cov: 32)
• Consequence: COX5A NM_004255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

Genes affected

COX5A (HGNC:2267): (cytochrome c oxidase subunit 5A) 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 of 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 Va of the human mitochondrial respiratory chain enzyme. A pseudogene COX5AP1 has been found in chromosome 14q22. [provided by RefSeq, Jul 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX5A	NM_004255.4	c.217+489G>A		intron_variant	Intron 2 of 4	ENST00000322347.11	NP_004246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX5A	ENST00000322347.11	c.217+489G>A		intron_variant	Intron 2 of 4	1	NM_004255.4	ENSP00000317780.6

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53608 AN: 152028 Hom.: 12237 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.352 AC: 53610 AN: 152146 Hom.: 12235 Cov.: 32 AF XY: 0.341 AC XY: 25360 AN XY: 74364

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.359

Alfa AF: 0.407 Hom.: 1766

Bravo AF: 0.349

Asia WGS AF: 0.120 AC: 421 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	2.5
DANN	Benign	0.60

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: rs11072513; hg19: chr15-75220968;