2-62049838-C-T

Position:

• chr2-62049838-C-T

Variant summary

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

The NM_152516.4(COMMD1):​c.462+48856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 152,020 control chromosomes in the GnomAD database, including 704 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 0.084 (704 hom., cov: 32)
• Consequence: COMMD1 NM_152516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

Genes affected

COMMD1 (HGNC:23024): (copper metabolism domain containing 1) Enables several functions, including phosphatidylinositol-3,4-bisphosphate binding activity; phospholipid binding activity; and protein homodimerization activity. Involved in several processes, including Golgi to plasma membrane transport; negative regulation of protein localization to cell surface; and regulation of cellular protein metabolic process. Acts upstream of or within negative regulation of NF-kappaB transcription factor activity. Located in cytosol; endosome; and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

COMMD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMMD1	NM_152516.4	c.462+48856C>T		intron_variant		ENST00000311832.6	NP_689729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMMD1	ENST00000311832.6	c.462+48856C>T		intron_variant		1	NM_152516.4	ENSP00000308236.5
COMMD1	ENST00000427417.1	c.3+48856C>T		intron_variant		5		ENSP00000413207.1
COMMD1	ENST00000458337.5	c.3+48856C>T		intron_variant		5		ENSP00000401236.1
COMMD1	ENST00000472729.1	n.401+48856C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12713 AN: 151902 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0906

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

GnomAD4 genome AF: 0.0836 AC: 12712 AN: 152020 Hom.: 704 Cov.: 32 AF XY: 0.0842 AC XY: 6257 AN XY: 74306

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.0492

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0897

Alfa AF: 0.102 Hom.: 1097

Bravo AF: 0.0707

Asia WGS AF: 0.0380 AC: 134 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.37

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: rs10518958; hg19: chr2-62276973;