rs1357338

Positions:

• chr1-175961750-A-G

Variant summary

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

The NM_022457.7(COP1):​c.2134-14511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 148,300 control chromosomes in the GnomAD database, including 63,221 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 0.92 (63221 hom., cov: 24)
• Consequence: COP1 NM_022457.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463

Genes affected

COP1 (HGNC:17440): (COP1 E3 ubiquitin ligase) Enables ubiquitin protein ligase activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and response to ionizing radiation. Part of Cul4A-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COP1	NM_022457.7	c.2134-14511T>C		intron_variant		ENST00000367669.8	NP_071902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COP1	ENST00000367669.8	c.2134-14511T>C		intron_variant		1	NM_022457.7	ENSP00000356641	P1

Frequencies

GnomAD3 genomes AF: 0.917 AC: 135856 AN: 148210 Hom.: 63206 Cov.: 24

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.916 AC: 135908 AN: 148300 Hom.: 63221 Cov.: 24 AF XY: 0.918 AC XY: 66001 AN XY: 71864

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.986

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.967

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.989

Gnomad4 OTH AF: 0.941

Alfa AF: 0.943 Hom.: 9865

Bravo AF: 0.907

Asia WGS AF: 0.973 AC: 3386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.86

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: rs1357338; hg19: chr1-175930886;