chrX-77902777-A-G

Position:

chrX-77902777-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001866.3(COX7B):c.165+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,198,203 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., 16 hem., cov: 23)

Exomes 𝑓: 0.000067 ( 0 hom. 13 hem. )

Consequence

COX7B
NM_001866.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.46

Variant links:

Genes affected

COX7B (HGNC:2291): (cytochrome c oxidase subunit 7B) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes subunit VIIb, which is highly similar to bovine COX VIIb protein and is found in all tissues. This gene may have several pseudogenes on chromosomes 1, 2, 20 and 22. [provided by RefSeq, Jun 2011]

COX7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051732063).

BP6

Variant X-77902777-A-G is Benign according to our data. Variant chrX-77902777-A-G is described in ClinVar as [Benign]. Clinvar id is 386711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX7B	NM_001866.3 linkuse as main transcript	c.165+10A>G		intron_variant		ENST00000650309.2	NP_001857.1	P24311

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COX7B	ENST00000650309.2 linkuse as main transcript	c.165+10A>G		intron_variant			NM_001866.3	ENSP00000497474.1	P24311
COX7B	ENST00000475465.1 linkuse as main transcript	c.175A>G	p.Ile59Val	missense_variant	2/2	2		ENSP00000497958.1	A0A3B3ITX0
COX7B	ENST00000373335.4 linkuse as main transcript	c.105+10A>G		intron_variant		2		ENSP00000496880.1	A0A3B3IRN8
COX7B	ENST00000647835.1 linkuse as main transcript	c.*38+10A>G		intron_variant				ENSP00000497517.1	A0A3B3ISY5

Frequencies

GnomAD3 genomes

AF:

0.000581

AC:

AN:

111800

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

33950

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000669

GnomAD3 exomes

AF:

0.000214

AC:

AN:

177817

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

62777

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.0000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000672

AC:

AN:

1086351

Hom.:

Cov.:

AF XY:

0.0000369

AC XY:

AN XY:

352781

show subpopulations

Gnomad4 AFR exome

AF:

0.00257

Gnomad4 AMR exome

AF:

0.0000580

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000359

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.000581

AC:

AN:

111852

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

34012

show subpopulations

Gnomad4 AFR

AF:

0.00208

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000654

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

COX7B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 13, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.46

DANN

Benign

0.78

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0052

GERP RS

-6.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over