chr1-160332545-C-T

Position:

• chr1-160332545-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_004371.4(COPA):​c.399G>A​(p.Gly133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 1,607,578 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G133G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00063 (8 hom.)
• Consequence: COPA NM_004371.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0730

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 1-160332545-C-T is Benign according to our data. Variant chr1-160332545-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-160332545-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.073 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000362 (55/152032) while in subpopulation SAS AF= 0.00333 (16/4812). AF 95% confidence interval is 0.00209. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPA	NM_004371.4	c.399G>A	p.Gly133=	synonymous_variant	6/33	ENST00000241704.8	NP_004362.2
COPA	NM_001098398.2	c.399G>A	p.Gly133=	synonymous_variant	6/33		NP_001091868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPA	ENST00000241704.8	c.399G>A	p.Gly133=	synonymous_variant	6/33	1	NM_004371.4	ENSP00000241704	P1

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 55 AN: 151914 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.000285

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00103 AC: 251 AN: 244436 Hom.: 1 AF XY: 0.00135 AC XY: 178 AN XY: 132060

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.0000911

Gnomad ASJ exome AF: 0.000202

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00724

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.000287

Gnomad OTH exome AF: 0.000336

GnomAD4 exome AF: 0.000627 AC: 912 AN: 1455546 Hom.: 8 Cov.: 30 AF XY: 0.000796 AC XY: 576 AN XY: 724002

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.0000926

Gnomad4 ASJ exome AF: 0.000500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00613

Gnomad4 FIN exome AF: 0.000207

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.000615

GnomAD4 genome AF: 0.000362 AC: 55 AN: 152032 Hom.: 0 Cov.: 31 AF XY: 0.000404 AC XY: 30 AN XY: 74316

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00333

Gnomad4 FIN AF: 0.000285

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000255 Hom.: 0

Bravo AF: 0.000314

EpiCase AF: 0.000383

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autoimmune interstitial lung disease-arthritis syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 13, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs142221638; hg19: chr1-160302335;