rs11726563

chr4-46821617-A-C

Variant summary

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

The NM_130902.3(COX7B2):c.-50+23343T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,196 control chromosomes in the GnomAD database, including 2,067 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 0.14 (2067 hom., cov: 32)
• Consequence: COX7B2 NM_130902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

Genes affected

COX7B2 (HGNC:24381): (cytochrome c oxidase subunit 7B2) Predicted to enable cytochrome-c oxidase activity. Predicted to be involved in electron transport chain; oxidative phosphorylation; and proton transmembrane transport. Predicted to be located in mitochondrial respirasome. Predicted to be integral component of membrane. Predicted to be part of respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX7B2	NM_130902.3	c.-50+23343T>G		intron_variant		ENST00000355591.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX7B2	ENST00000355591.8	c.-50+23343T>G		intron_variant		1	NM_130902.3	P4
COX7B2	ENST00000396533.5	c.-50+23343T>G		intron_variant		1		P4
COX7B2	ENST00000505102.1	c.-50+23343T>G		intron_variant		3
COX7B2	ENST00000543208.5	c.-53+23343T>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20706 AN: 152078 Hom.: 2060 Cov.: 32

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.0696

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.136 AC: 20722 AN: 152196 Hom.: 2067 Cov.: 32 AF XY: 0.145 AC XY: 10786 AN XY: 74404

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.0696

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.139

Alfa AF: 0.135 Hom.: 1017

Bravo AF: 0.139

Asia WGS AF: 0.183 AC: 636 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.35

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: rs11726563; hg19: chr4-46823634;