17-46923163-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004287.5(GOSR2):c.-30G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,448,982 control chromosomes in the GnomAD database, including 110,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10047 hom., cov: 33)

Exomes 𝑓: 0.39 ( 100207 hom. )

Consequence

GOSR2
NM_004287.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.997

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:

ENSG00000262633 (HGNC:):

ENSG00000262633 links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (BayesDel_noAF=-0.81).

BP6

Variant 17-46923163-G-C is Benign according to our data. Variant chr17-46923163-G-C is described in ClinVar as [Benign]. Clinvar id is 137487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46923163-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOSR2	NM_004287.5 link	c.-30G>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000640051.2	NP_004278.2	O14653-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GOSR2	ENST00000640051 link	c.-30G>C	5_prime_UTR_variant	Exon 1 of 6	1	NM_004287.5	ENSP00000492751.1	O14653-1
ENSG00000262633	ENST00000571841.1 link	n.-30G>C	non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000461460.1	E7EQ34
ENSG00000262633	ENST00000571841.1 link	n.-30G>C	5_prime_UTR_variant	Exon 1 of 10	5		ENSP00000461460.1	E7EQ34

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54605

AN:

152056

Hom.:

10048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.375

GnomAD3 exomes

AF:

0.396

AC:

60566

AN:

152982

Hom.:

12188

AF XY:

0.399

AC XY:

32421

AN XY:

81196

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.312

Gnomad EAS exome

AF:

0.426

Gnomad SAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.390

AC:

506282

AN:

1296808

Hom.:

100207

Cov.:

AF XY:

0.392

AC XY:

252690

AN XY:

644490

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.469

Gnomad4 SAS exome

AF:

0.456

Gnomad4 FIN exome

AF:

0.407

Gnomad4 NFE exome

AF:

0.387

Gnomad4 OTH exome

AF:

0.380

GnomAD4 genome

AF:

0.359

AC:

54627

AN:

152174

Hom.:

10047

Cov.:

AF XY:

0.363

AC XY:

27026

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.446

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.280

Hom.:

1108

Bravo

AF:

0.352

Asia WGS

AF:

0.440

AC:

1532

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 29, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 59% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 55. Only high quality variants are reported. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Progressive myoclonic epilepsy type 6

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Progressive myoclonic epilepsy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.8

DANN

Benign

0.57

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