rs12738115

Variant names:

• chr1-176192129-G-C
• rs12738115
• NM_022457.7:c.408-7437C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022457.7(COP1):​c.408-7437C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 152,060 control chromosomes in the GnomAD database, including 151 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 0.038 (151 hom., cov: 32)
• Consequence: COP1 NM_022457.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COP1	NM_022457.7	c.408-7437C>G		intron_variant	Intron 1 of 19	ENST00000367669.8	NP_071902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COP1	ENST00000367669.8	c.408-7437C>G		intron_variant	Intron 1 of 19	1	NM_022457.7	ENSP00000356641.3

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5768 AN: 151942 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.00998

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0379 AC: 5765 AN: 152060 Hom.: 151 Cov.: 32 AF XY: 0.0379 AC XY: 2820 AN XY: 74354

African (AFR) AF: 0.00993 AC: 412 AN: 41502

American (AMR) AF: 0.0381 AC: 581 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4826

European-Finnish (FIN) AF: 0.0634 AC: 671 AN: 10586

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3593 AN: 67926

Other (OTH) AF: 0.0427 AC: 90 AN: 2108

Alfa AF: 0.0433 Hom.: 21

Bravo AF: 0.0367

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		0.029
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12738115; hg19: chr1-176161265;