4-46874542-T-G

Variant names:

• chr4-46874542-T-G
• rs2036943
• NM_130902.3:c.-104-29528A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130902.3(COX7B2):​c.-104-29528A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: COX7B2 NM_130902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 2 publications found

Genes affected

COX7B2 (HGNC:24381): (cytochrome c oxidase subunit 7B2) Predicted to enable cytochrome-c oxidase activity. Predicted to be involved in electron transport chain; oxidative phosphorylation; and proton transmembrane transport. Predicted to be located in mitochondrial respirasome. Predicted to be integral component of membrane. Predicted to be part of respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299086 (HGNC:58780):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130902.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX7B2	NM_130902.3	MANE Select	c.-104-29528A>C		intron	N/A	NP_570972.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX7B2	ENST00000355591.8	TSL:1 MANE Select	c.-104-29528A>C		intron	N/A	ENSP00000347799.3
	COX7B2	ENST00000396533.5	TSL:1	c.-105+2097A>C		intron	N/A	ENSP00000379784.1
	COX7B2	ENST00000543208.5	TSL:5	c.-108+2097A>C		intron	N/A	ENSP00000437439.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		1.4

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: rs2036943; hg19: chr4-46876559;