4-46886099-A-G

Variant names:

• chr4-46886099-A-G
• rs7679715
• NM_130902.3:c.-105+23061T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130902.3(COX7B2):​c.-105+23061T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,056 control chromosomes in the GnomAD database, including 9,335 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 0.34 (9335 hom., cov: 32)
• Consequence: COX7B2 NM_130902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 7 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]

ENSG00000299086 (HGNC:58780):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 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.-105+23061T>C		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.-105+23061T>C		intron	N/A	ENSP00000347799.3	Q8TF08
	COX7B2	ENST00000396533.5	TSL:1	c.-203-9362T>C		intron	N/A	ENSP00000379784.1	Q8TF08
	COX7B2	ENST00000505102.1	TSL:3	c.-105+17777T>C		intron	N/A	ENSP00000423519.1	D6R9N1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52405 AN: 151938 Hom.: 9332 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.345 AC: 52431 AN: 152056 Hom.: 9335 Cov.: 32 AF XY: 0.338 AC XY: 25094 AN XY: 74316

African (AFR) AF: 0.315 AC: 13076 AN: 41516

American (AMR) AF: 0.246 AC: 3763 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1132 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1851 AN: 5162

South Asian (SAS) AF: 0.419 AC: 2021 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3203 AN: 10570

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26248 AN: 67926

Other (OTH) AF: 0.326 AC: 686 AN: 2106

Alfa AF: 0.360 Hom.: 5680

Bravo AF: 0.334

Asia WGS AF: 0.371 AC: 1285 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.46
PhyloP100		-0.69
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7679715;

hg19: chr4-46888116;