1-160342475-T-G

Position:

• chr1-160342475-T-G

Variant summary

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

The NM_004371.4(COPA):​c.40+656A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,004 control chromosomes in the GnomAD database, including 32,982 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 0.64 (32982 hom., cov: 31)
• Consequence: COPA NM_004371.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

COPA (HGNC:2230): (COPI coat complex subunit alpha) In eukaryotic cells, protein transport between the endoplasmic reticulum and Golgi compartments is mediated in part by non-clathrin-coated vesicular coat proteins (COPs). Seven coat proteins have been identified, and they represent subunits of a complex known as coatomer. The subunits are designated alpha-COP, beta-COP, beta-prime-COP, gamma-COP, delta-COP, epsilon-COP, and zeta-COP. The alpha-COP, encoded by COPA, shares high sequence similarity with RET1P, the alpha subunit of the coatomer complex in yeast. Also, the N-terminal 25 amino acids of alpha-COP encode the bioactive peptide, xenin, which stimulates exocrine pancreatic secretion and may act as a gastrointestinal hormone. Alternative splicing results in multiple splice forms encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPA	NM_004371.4	c.40+656A>C		intron_variant		ENST00000241704.8	NP_004362.2
COPA	NM_001098398.2	c.40+656A>C		intron_variant			NP_001091868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPA	ENST00000241704.8	c.40+656A>C		intron_variant		1	NM_004371.4	ENSP00000241704	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97680 AN: 151886 Hom.: 32934 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.643 AC: 97787 AN: 152004 Hom.: 32982 Cov.: 31 AF XY: 0.640 AC XY: 47544 AN XY: 74278

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.641

Alfa AF: 0.570 Hom.: 28022

Bravo AF: 0.654

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10752637; hg19: chr1-160312265;