X-77902417-A-G

Position:

• chrX-77902417-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001866.3(COX7B):​c.41-226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 112,183 control chromosomes in the GnomAD database, including 10 homozygotes. There are 228 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0070 (10 hom., 228 hem., cov: 23)
• Consequence: COX7B NM_001866.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.635

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-77902417-A-G is Benign according to our data. Variant chrX-77902417-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1318137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX7B	NM_001866.3	c.41-226A>G		intron_variant		ENST00000650309.2	NP_001857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX7B	ENST00000650309.2	c.41-226A>G		intron_variant			NM_001866.3	ENSP00000497474.1
COX7B	ENST00000373335.4	c.-20-226A>G		intron_variant		2		ENSP00000496880.1
COX7B	ENST00000475465.1	c.41-226A>G		intron_variant		2		ENSP00000497958.1
COX7B	ENST00000647835.1	c.41-233A>G		intron_variant				ENSP00000497517.1

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 785 AN: 112131 Hom.: 10 Cov.: 23 AF XY: 0.00664 AC XY: 228 AN XY: 34327

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.000756

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00132

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

GnomAD4 genome AF: 0.00700 AC: 785 AN: 112183 Hom.: 10 Cov.: 23 AF XY: 0.00663 AC XY: 228 AN XY: 34389

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.000756

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.00745 Hom.: 40

Bravo AF: 0.00575

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.77

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: rs186551143; hg19: chrX-77157914;