rs2036943

chr4-46874542-T-Achr4-46874542-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_130902.3(COX7B2):c.-104-29528A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,064 control chromosomes in the GnomAD database, including 6,706 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 0.29 (6706 hom., cov: 32)
• Consequence: COX7B2 NM_130902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX7B2	NM_130902.3	c.-104-29528A>T		intron_variant		ENST00000355591.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX7B2	ENST00000355591.8	c.-104-29528A>T		intron_variant		1	NM_130902.3	P4
COX7B2	ENST00000396533.5	c.-105+2097A>T		intron_variant		1		P4
COX7B2	ENST00000505102.1	c.-105+29334A>T		intron_variant		3
COX7B2	ENST00000543208.5	c.-108+2097A>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43996 AN: 151946 Hom.: 6689 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.290 AC: 44050 AN: 152064 Hom.: 6706 Cov.: 32 AF XY: 0.295 AC XY: 21941 AN XY: 74336

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.259

Alfa AF: 0.194 Hom.: 477

Bravo AF: 0.285

Asia WGS AF: 0.362 AC: 1260 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
Cadd	Benign	10
Dann	Benign	0.90

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: rs2036943; hg19: chr4-46876559; COSMIC: COSV57218205;