17-46966142-T-C

Position:

• chr17-46966142-T-C

Variant summary

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

The NM_001321133.2(GOSR2):​c.584-392T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,210 control chromosomes in the GnomAD database, including 2,184 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 0.15 (2184 hom., cov: 32)
• Consequence: GOSR2 NM_001321133.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOSR2	NM_001321133.2	c.584-392T>C		intron_variant			NP_001308062.1
GOSR2	XM_017025378.2	c.581-392T>C		intron_variant			XP_016880867.1
GOSR2	XM_017025383.3	c.584-392T>C		intron_variant			XP_016880872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000573224.2	c.584-392T>C		intron_variant		5		ENSP00000461784
GOSR2	ENST00000640723.1	c.523-392T>C		intron_variant		5		ENSP00000492206
GOSR2	ENST00000638189.1	c.*847-392T>C		intron_variant, NMD_transcript_variant		5		ENSP00000491785

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23263 AN: 152092 Hom.: 2190 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.153 AC: 23250 AN: 152210 Hom.: 2184 Cov.: 32 AF XY: 0.156 AC XY: 11585 AN XY: 74410

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0884

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.162

Alfa AF: 0.177 Hom.: 2424

Bravo AF: 0.146

Asia WGS AF: 0.166 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.53

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: rs16941382; hg19: chr17-45043508;