rs17598636

Positions:

• chr4-46851197-T-C

Variant summary

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

The ENST00000355591.8(COX7B2):​c.-104-6183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 152,076 control chromosomes in the GnomAD database, including 312 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 0.057 (312 hom., cov: 32)
• Consequence: COX7B2 ENST00000355591.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX7B2	NM_130902.3	c.-104-6183A>G		intron_variant		ENST00000355591.8	NP_570972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX7B2	ENST00000355591.8	c.-104-6183A>G		intron_variant		1	NM_130902.3	ENSP00000347799	P4
COX7B2	ENST00000396533.5	c.-104-6183A>G		intron_variant		1		ENSP00000379784	P4
COX7B2	ENST00000505102.1	c.-104-6183A>G		intron_variant		3		ENSP00000423519
COX7B2	ENST00000543208.5	c.-107-6183A>G		intron_variant		5		ENSP00000437439	A1

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8613 AN: 151958 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.0999

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0566 AC: 8612 AN: 152076 Hom.: 312 Cov.: 32 AF XY: 0.0580 AC XY: 4314 AN XY: 74322

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0945

Gnomad4 EAS AF: 0.0997

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0644 Hom.: 255

Bravo AF: 0.0537

Asia WGS AF: 0.148 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.46

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: rs17598636; hg19: chr4-46853214;