1-160290161-C-T

Position:

chr1-160290161-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP6_ModerateBS1BS2

The NM_004371.4(COPA):c.3671G>A(p.Arg1224His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,613,894 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000068 ( 1 hom. )

Consequence

COPA
NM_004371.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.24

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:

LOC107985219 (HGNC:):

LOC107985219 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), COPA. . Gene score misZ 3.558 (greater than the threshold 3.09). Trascript score misZ 4.7888 (greater than threshold 3.09). GenCC has associacion of gene with autoimmune interstitial lung disease-arthritis syndrome.

BP6

Variant 1-160290161-C-T is Benign according to our data. Variant chr1-160290161-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2914457.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000329 (5/152094) while in subpopulation SAS AF= 0.000828 (4/4830). AF 95% confidence interval is 0.000282. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COPA	NM_004371.4 linkuse as main transcript	c.3671G>A	p.Arg1224His	missense_variant	33/33	ENST00000241704.8	NP_004362.2
LOC107985219	XR_001738265.2 linkuse as main transcript	n.537-1096C>T		intron_variant, non_coding_transcript_variant
COPA	NM_001098398.2 linkuse as main transcript	c.3698G>A	p.Arg1233His	missense_variant	33/33		NP_001091868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPA	ENST00000241704.8 linkuse as main transcript	c.3671G>A	p.Arg1224His	missense_variant	33/33	1	NM_004371.4	ENSP00000241704	P1	P53621-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

250306

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autoimmune interstitial lung disease-arthritis syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

.;.;T;.;.

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.56

D;D;D;D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

2.9

.;.;M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.1

.;D;D;.;.

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

.;D;D;.;.

Sift4G

Uncertain

0.0030

.;D;D;.;.

Polyphen

1.0

.;D;D;.;.

Vest4

0.69, 0.68

MutPred

0.73

.;.;Loss of MoRF binding (P = 0.0092);.;.;

MVP

0.67

MPC

1.5

ClinPred

0.84

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.63

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

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