rs11726563

Variant names:

• chr4-46821617-A-C
• rs11726563
• NM_130902.3:c.-50+23343T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130902.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX7B2	NM_130902.3	MANE Select	c.-50+23343T>G		intron	N/A	NP_570972.2	Q8TF08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX7B2	ENST00000355591.8	TSL:1 MANE Select	c.-50+23343T>G		intron	N/A	ENSP00000347799.3	Q8TF08
	COX7B2	ENST00000396533.5	TSL:1	c.-50+23343T>G		intron	N/A	ENSP00000379784.1	Q8TF08
	COX7B2	ENST00000543208.5	TSL:5	c.-53+23343T>G		intron	N/A	ENSP00000437439.1	A0A0C4DGG2

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

African (AFR) AF: 0.0322 AC: 1340 AN: 41552

American (AMR) AF: 0.297 AC: 4535 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0696 AC: 241 AN: 3464

East Asian (EAS) AF: 0.290 AC: 1497 AN: 5162

South Asian (SAS) AF: 0.110 AC: 529 AN: 4828

European-Finnish (FIN) AF: 0.244 AC: 2578 AN: 10574

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9631 AN: 68012

Other (OTH) AF: 0.139 AC: 295 AN: 2116

Alfa AF: 0.137 Hom.: 1244

Bravo AF: 0.139

Asia WGS AF: 0.183 AC: 636 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		-0.013
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: rs11726563; hg19: chr4-46823634;