chr1-160332545-C-T

Variant names:

• chr1-160332545-C-T
• rs142221638
• NM_004371.4:c.399G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_004371.4(COPA):​c.399G>A​(p.Gly133Gly) 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:3
• Conservation: PhyloP100: -0.0730
• Publications: 0 publications found

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]

COPA Gene-Disease associations (from GenCC):

• autoimmune interstitial lung disease-arthritis syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 542645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 55 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004371.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPA	NM_004371.4	MANE Select	c.399G>A	p.Gly133Gly	synonymous	Exon 6 of 33	NP_004362.2	P53621-1
	COPA	NM_001098398.2		c.399G>A	p.Gly133Gly	synonymous	Exon 6 of 33	NP_001091868.1	P53621-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COPA	ENST00000241704.8	TSL:1 MANE Select	c.399G>A	p.Gly133Gly	synonymous	Exon 6 of 33	ENSP00000241704.7	P53621-1
	COPA	ENST00000368069.7	TSL:1	c.399G>A	p.Gly133Gly	synonymous	Exon 6 of 33	ENSP00000357048.3	P53621-2
	COPA	ENST00000971414.1		c.393G>A	p.Gly131Gly	synonymous	Exon 6 of 33	ENSP00000641473.1

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

GnomAD2 exomes AF: 0.00103 AC: 251 AN: 244436 AF XY: 0.00135

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 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

African (AFR) AF: 0.000121 AC: 4 AN: 33086

American (AMR) AF: 0.0000926 AC: 4 AN: 43182

Ashkenazi Jewish (ASJ) AF: 0.000500 AC: 13 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00613 AC: 519 AN: 84650

European-Finnish (FIN) AF: 0.000207 AC: 11 AN: 53106

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5734

European-Non Finnish (NFE) AF: 0.000281 AC: 312 AN: 1110032

Other (OTH) AF: 0.000615 AC: 37 AN: 60160

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

African (AFR) AF: 0.000145 AC: 6 AN: 41476

American (AMR) AF: 0.000393 AC: 6 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.00333 AC: 16 AN: 4812

European-Finnish (FIN) AF: 0.000285 AC: 3 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67984

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000255 Hom.: 0

Bravo AF: 0.000314

EpiCase AF: 0.000383

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Autoimmune interstitial lung disease-arthritis syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		-0.073
PromoterAI		-0.0055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=86/14	polymorphism

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: rs142221638; hg19: chr1-160302335;