rs2178692

Positions:

• chr12-6726885-G-T

Variant summary

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

The NM_001164094.2(COPS7A):​c.163-1041G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,108 control chromosomes in the GnomAD database, including 42,238 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 0.74 (42238 hom., cov: 32)
• Consequence: COPS7A NM_001164094.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

Genes affected

COPS7A (HGNC:16758): (COP9 signalosome subunit 7A) This gene encodes a component of the COP9 signalosome, an evolutionarily conserved multi-subunit protease that regulates the activity of the ubiquitin conjugation pathway. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Mar 2014]

COPS7A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPS7A	NM_001164094.2	c.163-1041G>T		intron_variant		ENST00000543155.6	NP_001157566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPS7A	ENST00000543155.6	c.163-1041G>T		intron_variant		1	NM_001164094.2	ENSP00000438115.1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113042 AN: 151990 Hom.: 42222 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.744 AC: 113107 AN: 152108 Hom.: 42238 Cov.: 32 AF XY: 0.749 AC XY: 55680 AN XY: 74380

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.751

Alfa AF: 0.738 Hom.: 79415

Bravo AF: 0.737

Asia WGS AF: 0.832 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.78

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: rs2178692; hg19: chr12-6836051;