17-46923163-G-C

Variant names:

• chr17-46923163-G-C
• rs189899
• NM_004287.5:c.-30G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.997

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]

ENSG00000262633 (HGNC:):

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]

GOSR2-DT (HGNC:55346): (GOSR2 divergent transcript)

ACMG classification

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	c.-30G>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000640051.2	NP_004278.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54605 AN: 152056 Hom.: 10048 Cov.: 33

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

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.: 20 AF XY: 0.392 AC XY: 252690 AN XY: 644490

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.: 33 AF XY: 0.363 AC XY: 27026 AN XY: 74382

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

Submissions by phenotype

not specified Benign:4

-

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. -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs189899; hg19: chr17-45000529; COSMIC: COSV56661545; COSMIC: COSV56661545;