rs222471

chr2-42410917-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000423797.2(COX7A2L):n.398+2782A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,200 control chromosomes in the GnomAD database, including 1,669 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 0.15 (1669 hom., cov: 32)
• Consequence: COX7A2L ENST00000423797.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

Genes affected

COX7A2L (HGNC:2289): (cytochrome c oxidase subunit 7A2 like) 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 a protein similar to polypeptides 1 and 2 of subunit VIIa in the C-terminal region, and also highly similar to the mouse Sig81 protein sequence. This gene is expressed in all tissues, and upregulated in a breast cancer cell line after estrogen treatment. It is possible that this gene represents a regulatory subunit of COX and mediates the higher level of energy production in target cells by estrogen. Several transcript variants, some protein-coding and others non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

KCNG3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNG3	XR_007069666.1	n.1317+2782A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX7A2L	ENST00000423797.2	n.398+2782A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22200 AN: 152082 Hom.: 1665 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.146 AC: 22220 AN: 152200 Hom.: 1669 Cov.: 32 AF XY: 0.144 AC XY: 10732 AN XY: 74412

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.134

Alfa AF: 0.139 Hom.: 2583

Bravo AF: 0.148

Asia WGS AF: 0.153 AC: 535 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.1
Dann	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs222471; hg19: chr2-42638057;