19-35651137-A-G

Position:

• chr19-35651137-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001863.5(COX6B1):​c.-11-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 783,012 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (9 hom.)
• Consequence: COX6B1 NM_001863.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.331

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=-0.89).
• BP6: Variant 19-35651137-A-G is Benign according to our data. Variant chr19-35651137-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1186690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00898 (1367/152214) while in subpopulation AFR AF= 0.0304 (1262/41532). AF 95% confidence interval is 0.029. There are 26 homozygotes in gnomad4. There are 644 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX6B1	NM_001863.5	c.-11-96A>G		intron_variant		ENST00000649813.2	NP_001854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX6B1	ENST00000649813.2	c.-11-96A>G		intron_variant			NM_001863.5	ENSP00000497926.1
COX6B1	ENST00000652250.1	c.-107A>G		5_prime_UTR_variant	1/2			ENSP00000498883.1
COX6B1	ENST00000392201.1	c.-11-96A>G		intron_variant		3		ENSP00000376037.2
COX6B1	ENST00000592141.6	c.-11-96A>G		intron_variant		3		ENSP00000466818.2

Frequencies

GnomAD3 genomes AF: 0.00895 AC: 1362 AN: 152098 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.00159 AC: 1003 AN: 630798 Hom.: 9 AF XY: 0.00131 AC XY: 449 AN XY: 342182

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.000532

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000592

Gnomad4 FIN exome AF: 0.0000224

Gnomad4 NFE exome AF: 0.000486

Gnomad4 OTH exome AF: 0.00389

GnomAD4 genome AF: 0.00898 AC: 1367 AN: 152214 Hom.: 26 Cov.: 32 AF XY: 0.00865 AC XY: 644 AN XY: 74422

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00742 Hom.: 2

Bravo AF: 0.0101

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.33

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: rs116268200; hg19: chr19-36142039;