17-46949545-C-T

Position:

• chr17-46949545-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321133.2(GOSR2):​c.583+10841C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,032 control chromosomes in the GnomAD database, including 9,136 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9136 hom., cov: 32)
• Consequence: GOSR2 NM_001321133.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

Genes affected

ENSG00000262633 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOSR2	XM_047437112.1	c.*631C>T		3_prime_UTR_variant	9/9		XP_047293068.1
GOSR2	XM_047437113.1	c.*631C>T		3_prime_UTR_variant	9/9		XP_047293069.1
GOSR2	XM_017025389.2	c.*631C>T		3_prime_UTR_variant	9/9		XP_016880878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000262633	ENST00000571841.1	n.583+10841C>T		intron_variant		5		ENSP00000461460.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50321 AN: 151914 Hom.: 9139 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.357

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50330 AN: 152032 Hom.: 9136 Cov.: 32 AF XY: 0.337 AC XY: 25070 AN XY: 74306

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.358

Alfa AF: 0.316 Hom.: 1968

Bravo AF: 0.320

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.41

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: rs9911967; hg19: chr17-45026911;