11-63975948-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004074.3(COX8A):c.115-277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,040 control chromosomes in the GnomAD database, including 7,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (7380 hom., cov: 32)
• Consequence: COX8A NM_004074.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.204

Genes affected

COX8A (HGNC:2294): (cytochrome c oxidase subunit 8A) The protein encoded by this gene is the terminal enzyme of the respiratory chain, coupling the transfer of electrons from cytochrome c to molecular oxygen, with the concomitant production of a proton electrochemical gradient across the inner mitochondrial membrane. In addition to 3 mitochondrially encoded subunits, which perform the catalytic function, the eukaryotic enzyme contains nuclear-encoded smaller subunits, ranging in number from 4 in some organisms to 10 in mammals. It has been proposed that nuclear-encoded subunits may be involved in the modulation of the catalytic function. This gene encodes one of the nuclear-encoded subunits. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-63975948-A-G is Benign according to our data. Variant chr11-63975948-A-G is described in ClinVar as [Benign]. Clinvar id is 683608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX8A	NM_004074.3	c.115-277A>G		intron_variant		ENST00000314133.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX8A	ENST00000314133.4	c.115-277A>G		intron_variant		1	NM_004074.3	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42031 AN: 151922 Hom.: 7373 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.277 AC: 42041 AN: 152040 Hom.: 7380 Cov.: 32 AF XY: 0.275 AC XY: 20428 AN XY: 74294

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.0477

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.280

Alfa AF: 0.355 Hom.: 9753

Bravo AF: 0.252

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.1
Dann	Benign	0.72

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: rs11605797; hg19: chr11-63743420;