Variant chr1-160335254-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004371.4(COPA):c.297G>A(p.Thr99Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,608,976 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 32 hom. )

Consequence

COPA
NM_004371.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.46

Variant links:

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 links:

COPA (HGNC:):

COPA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-160335254-C-T is Benign according to our data. Variant chr1-160335254-C-T is described in ClinVar as [Benign]. Clinvar id is 476027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-160335254-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00177 (270/152176) while in subpopulation EAS AF= 0.0243 (126/5184). AF 95% confidence interval is 0.0209. There are 3 homozygotes in gnomad4. There are 139 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 270 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPA	NM_004371.4 linkuse as main transcript	c.297G>A	p.Thr99Thr	synonymous_variant	4/33	ENST00000241704.8	NP_004362.2	P53621-1
COPA	NM_001098398.2 linkuse as main transcript	c.297G>A	p.Thr99Thr	synonymous_variant	4/33		NP_001091868.1	P53621-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPA	ENST00000241704.8 linkuse as main transcript	c.297G>A	p.Thr99Thr	synonymous_variant	4/33	1	NM_004371.4	ENSP00000241704.7		P53621-1

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

270

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0246

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00468

AC:

1153

AN:

246582

Hom.:

AF XY:

0.00371

AC XY:

494

AN XY:

133304

show subpopulations

Gnomad AFR exome

AF:

0.000818

Gnomad AMR exome

AF:

0.0210

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0207

Gnomad SAS exome

AF:

0.000674

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.00333

GnomAD4 exome

AF:

0.00160

AC:

2330

AN:

1456800

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1043

AN XY:

724506

show subpopulations

Gnomad4 AFR exome

AF:

0.000391

Gnomad4 AMR exome

AF:

0.0188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0331

Gnomad4 SAS exome

AF:

0.000516

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000568

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00177

AC:

270

AN:

152176

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00498

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0243

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.00288

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autoimmune interstitial lung disease-arthritis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.34

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over