17-46923199-C-A

Position:

chr17-46923199-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004287.5(GOSR2):c.7C>A(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,546,906 control chromosomes in the GnomAD database, including 534 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 45 hom., cov: 33)

Exomes 𝑓: 0.024 ( 489 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.947

Variant links:

Genes affected

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

GOSR2 links:

LRRC37A2 (HGNC:):

LRRC37A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032203794).

BP6

Variant 17-46923199-C-A is Benign according to our data. Variant chr17-46923199-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 137488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46923199-C-A is described in Lovd as [Benign]. Variant chr17-46923199-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0181 (2765/152350) while in subpopulation NFE AF= 0.0235 (1602/68044). AF 95% confidence interval is 0.0226. There are 45 homozygotes in gnomad4. There are 1391 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOSR2	NM_004287.5 linkuse as main transcript	c.7C>A	p.Pro3Thr	missense_variant	1/6	ENST00000640051.2	NP_004278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2 linkuse as main transcript	c.7C>A	p.Pro3Thr	missense_variant	1/6	1	NM_004287.5	ENSP00000492751	P3	O14653-1

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2766

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0180

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0236

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0224

AC:

3462

AN:

154338

Hom.:

AF XY:

0.0237

AC XY:

1938

AN XY:

81616

show subpopulations

Gnomad AFR exome

AF:

0.00334

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.000621

Gnomad SAS exome

AF:

0.0256

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0249

GnomAD4 exome

AF:

0.0235

AC:

32809

AN:

1394556

Hom.:

489

Cov.:

AF XY:

0.0238

AC XY:

16356

AN XY:

688094

show subpopulations

Gnomad4 AFR exome

AF:

0.00349

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0657

Gnomad4 EAS exome

AF:

0.00193

Gnomad4 SAS exome

AF:

0.0253

Gnomad4 FIN exome

AF:

0.0289

Gnomad4 NFE exome

AF:

0.0240

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0181

AC:

2765

AN:

152350

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1391

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00433

Gnomad4 AMR

AF:

0.0179

Gnomad4 ASJ

AF:

0.0683

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0301

Gnomad4 NFE

AF:

0.0235

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0222

Hom.:

Bravo

AF:

0.0164

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.00345

AC:

ESP6500EA

AF:

0.0179

AC:

116

ExAC

AF:

0.0171

AC:

539

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 01, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 07, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Progressive myoclonic epilepsy

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2017

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0045

.;.;.;.;.;.;T;.;.;.;.;.;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.41

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0032

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.59

.;.;.;N;.;.;N;.;N;.;.;.;.;.

MutationTaster

Benign

0.69

D;D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.1

.;.;.;N;N;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.13

Sift

Benign

1.0

.;.;.;T;T;.;.;.;.;.;.;.;.;.

Sift4G

Benign

1.0

.;.;.;T;T;T;.;.;.;.;T;.;.;.

Polyphen

0.0

.;.;.;B;.;.;B;.;.;.;.;.;.;.

Vest4

0.23, 0.22, 0.090, 0.23

MPC

0.19

ClinPred

0.0083

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.052

gMVP

0.10

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