chr19-35654377-T-C

Position:

• chr19-35654377-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001863.5(COX6B1):​c.107-194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 152,056 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.040 (214 hom., cov: 32)
• Consequence: COX6B1 NM_001863.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.49

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 19-35654377-T-C is Benign according to our data. Variant chr19-35654377-T-C is described in ClinVar as [Benign]. Clinvar id is 1225325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX6B1	NM_001863.5	c.107-194T>C		intron_variant		ENST00000649813.2	NP_001854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX6B1	ENST00000649813.2	c.107-194T>C		intron_variant			NM_001863.5	ENSP00000497926.1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6118 AN: 151938 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.00723

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0413

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

GnomAD4 genome AF: 0.0404 AC: 6138 AN: 152056 Hom.: 214 Cov.: 32 AF XY: 0.0399 AC XY: 2966 AN XY: 74342

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.00723

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0316

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0442

Alfa AF: 0.00245 Hom.: 0

Bravo AF: 0.0440

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.38

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: rs142980738; hg19: chr19-36145279;