chr17-46923192-C-T

Variant names:

• chr17-46923192-C-T
• rs574045746
• NM_004287.5:c.-1C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004287.5(GOSR2):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,545,088 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (4 hom.)
• Consequence: GOSR2 NM_004287.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.00800
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000197 (30/152326) while in subpopulation SAS AF = 0.00207 (10/4826). AF 95% confidence interval is 0.00112. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004287.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	NM_004287.5	MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 6	NP_004278.2
	GOSR2	NM_001321133.2		c.-1C>T		5_prime_UTR	Exon 1 of 7	NP_001308062.1	I3NI02
	GOSR2	NM_054022.4		c.-1C>T		5_prime_UTR	Exon 1 of 7	NP_473363.1	O14653-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 6	ENSP00000492751.1	O14653-1
	GOSR2	ENST00000225567.9	TSL:1	c.-1C>T		5_prime_UTR	Exon 1 of 7	ENSP00000225567.4	O14653-2
	GOSR2	ENST00000640621.1	TSL:1	c.-1C>T		5_prime_UTR	Exon 1 of 5	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000441 AC: 68 AN: 154258 AF XY: 0.000576

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000888

Gnomad FIN exome AF: 0.000196

Gnomad NFE exome AF: 0.000271

Gnomad OTH exome AF: 0.000686

GnomAD4 exome AF: 0.000280 AC: 390 AN: 1392762 Hom.: 4 Cov.: 30 AF XY: 0.000356 AC XY: 245 AN XY: 687358

African (AFR) AF: 0.00 AC: 0 AN: 31476

American (AMR) AF: 0.0000840 AC: 3 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25118

East Asian (EAS) AF: 0.00 AC: 0 AN: 35700

South Asian (SAS) AF: 0.00183 AC: 145 AN: 79090

European-Finnish (FIN) AF: 0.000305 AC: 15 AN: 49132

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5664

European-Non Finnish (NFE) AF: 0.000203 AC: 218 AN: 1073144

Other (OTH) AF: 0.000139 AC: 8 AN: 57744

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000262 Hom.: 0

Bravo AF: 0.0000831

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.6
DANN	Benign	0.89
PhyloP100		-0.0080
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs574045746; hg19: chr17-45000558;