rs2178692

Variant names:

• chr12-6726885-G-T
• rs2178692
• NM_001164094.2:c.163-1041G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164094.2. 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
	COPS7A	NM_001164094.2	MANE Select	c.163-1041G>T		intron	N/A	NP_001157566.1
	COPS7A	NM_001164093.2		c.163-1041G>T		intron	N/A	NP_001157565.1
	COPS7A	NM_001164095.3		c.163-1041G>T		intron	N/A	NP_001157567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPS7A	ENST00000543155.6	TSL:1 MANE Select	c.163-1041G>T		intron	N/A	ENSP00000438115.1
	COPS7A	ENST00000229251.7	TSL:1	c.163-1041G>T		intron	N/A	ENSP00000229251.3
	COPS7A	ENST00000534947.5	TSL:1	c.163-1041G>T		intron	N/A	ENSP00000446039.1

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

African (AFR) AF: 0.718 AC: 29761 AN: 41468

American (AMR) AF: 0.756 AC: 11558 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2827 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4214 AN: 5186

South Asian (SAS) AF: 0.920 AC: 4446 AN: 4832

European-Finnish (FIN) AF: 0.769 AC: 8126 AN: 10566

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49668 AN: 67990

Other (OTH) AF: 0.751 AC: 1588 AN: 2114

Alfa AF: 0.735 Hom.: 158921

Bravo AF: 0.737

Asia WGS AF: 0.832 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

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: rs2178692; hg19: chr12-6836051;