20-31638740-C-G

Position:

• chr20-31638740-C-G

Variant summary

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

The ENST00000376075.4(COX4I2):​c.1-278C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,914 control chromosomes in the GnomAD database, including 8,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (8264 hom., cov: 31)
• Consequence: COX4I2 ENST00000376075.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.185

Genes affected

COX4I2 (HGNC:16232): (cytochrome c oxidase subunit 4I2) 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 isoform 2 of subunit IV. Isoform 1 of subunit IV is encoded by a different gene, however, the two genes show a similar structural organization. Subunit IV is the largest nuclear encoded subunit which plays a pivotal role in COX regulation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-31638740-C-G is Benign according to our data. Variant chr20-31638740-C-G is described in ClinVar as [Benign]. Clinvar id is 1258594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX4I2	NM_032609.3	c.1-278C>G		intron_variant		ENST00000376075.4	NP_115998.2
COX4I2	XM_005260581.4	c.1-278C>G		intron_variant			XP_005260638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX4I2	ENST00000376075.4	c.1-278C>G		intron_variant		1	NM_032609.3	ENSP00000365243	P1
COX4I2	ENST00000490030.1	n.31-278C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43733 AN: 151794 Hom.: 8264 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.000584

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.288 AC: 43762 AN: 151914 Hom.: 8264 Cov.: 31 AF XY: 0.285 AC XY: 21130 AN XY: 74260

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.000585

Gnomad4 SAS AF: 0.0655

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.250

Alfa AF: 0.262 Hom.: 778

Bravo AF: 0.298

Asia WGS AF: 0.0640 AC: 225 AN: 3478

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 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.62

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: rs6088856; hg19: chr20-30226543;