rs2752

Variant names:

• chr1-234378125-C-A
• rs2752
• NM_001206641.3:c.372+3736C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-234378125-C-A
• chr1-234378125-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206641.3(COA6):​c.372+3736C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,964 control chromosomes in the GnomAD database, including 24,356 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24356 hom., cov: 32)
• Consequence: COA6 NM_001206641.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 13 publications found

Genes affected

COA6 (HGNC:18025): (cytochrome c oxidase assembly factor 6) This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

COA6 Gene-Disease associations (from GenCC):

• cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4

  Inheritance: AR, Unknown Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COA6	NM_001206641.3	c.372+3736C>A		intron_variant	Intron 2 of 2	ENST00000366615.10	NP_001193570.2
COA6	NM_001012985.2	c.282+3736C>A		intron_variant	Intron 2 of 2		NP_001013003.1
COA6	NM_001301733.1	c.144+3736C>A		intron_variant	Intron 1 of 1		NP_001288662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COA6	ENST00000366615.10	c.372+3736C>A		intron_variant	Intron 2 of 2	1	NM_001206641.3	ENSP00000355574.5
COA6	ENST00000366613.1	c.282+3736C>A		intron_variant	Intron 2 of 2	1		ENSP00000355572.1
COA6	ENST00000366612.1	c.144+3736C>A		intron_variant	Intron 1 of 1	1		ENSP00000355571.1
COA6	ENST00000619305.1	c.144+3736C>A		intron_variant	Intron 2 of 2	1		ENSP00000479686.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82912 AN: 151844 Hom.: 24308 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.546 AC: 83008 AN: 151964 Hom.: 24356 Cov.: 32 AF XY: 0.540 AC XY: 40091 AN XY: 74266

African (AFR) AF: 0.766 AC: 31780 AN: 41472

American (AMR) AF: 0.595 AC: 9091 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1699 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2482 AN: 5156

South Asian (SAS) AF: 0.364 AC: 1756 AN: 4820

European-Finnish (FIN) AF: 0.356 AC: 3748 AN: 10522

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30862 AN: 67940

Other (OTH) AF: 0.531 AC: 1121 AN: 2112

Alfa AF: 0.490 Hom.: 51338

Bravo AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.56
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2752; hg19: chr1-234513871;