Variant chr19-35651394-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001863.5(COX6B1):c.106+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,463,866 control chromosomes in the GnomAD database, including 10,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1038 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9232 hom. )

Consequence

COX6B1
NM_001863.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.188

Variant links:

Genes affected

COX6B1 (HGNC:2280): (cytochrome c oxidase subunit 6B1) Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It 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 be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIb. Mutations in this gene are associated with severe infantile encephalomyopathy. Three pseudogenes COX6BP-1, COX6BP-2 and COX6BP-3 have been found on chromosomes 7, 17 and 22q13.1-13.2, respectively. [provided by RefSeq, Jan 2010]

COX6B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-35651394-G-A is Benign according to our data. Variant chr19-35651394-G-A is described in ClinVar as [Benign]. Clinvar id is 676113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX6B1	NM_001863.5 linkuse as main transcript	c.106+45G>A		intron_variant		ENST00000649813.2	NP_001854.1	P14854

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX6B1	ENST00000649813.2 linkuse as main transcript	c.106+45G>A		intron_variant			NM_001863.5	ENSP00000497926.1		P14854

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17000

AN:

151818

Hom.:

1037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0781

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.132

AC:

31877

AN:

240650

Hom.:

2343

AF XY:

0.129

AC XY:

16802

AN XY:

130402

show subpopulations

Gnomad AFR exome

AF:

0.0787

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.0551

Gnomad EAS exome

AF:

0.127

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.113

AC:

148131

AN:

1311930

Hom.:

9232

Cov.:

AF XY:

0.113

AC XY:

74513

AN XY:

659910

show subpopulations

Gnomad4 AFR exome

AF:

0.0765

Gnomad4 AMR exome

AF:

0.209

Gnomad4 ASJ exome

AF:

0.0571

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.112

AC:

17019

AN:

151936

Hom.:

1038

Cov.:

AF XY:

0.116

AC XY:

8605

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0781

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0773

Hom.:

141

Bravo

AF:

0.107

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

DANN

Benign

0.53

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