17-46923163-G-C

Position:

• chr17-46923163-G-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]

LRRC37A2 (HGNC:):

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/exons	MANE	UniProt
GOSR2	NM_004287.5	c.-30G>C		5_prime_UTR_variant	1/6	ENST00000640051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOSR2	ENST00000640051.2	c.-30G>C		5_prime_UTR_variant	1/6	1	NM_004287.5	P3

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

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 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, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Progressive myoclonic epilepsy type 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Progressive myoclonic epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;