chr17-46928464-G-A

Variant names:

• chr17-46928464-G-A
• rs3785889
• NM_004287.5:c.30-1056G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004287.5(GOSR2):​c.30-1056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,842 control chromosomes in the GnomAD database, including 15,847 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 0.45 (15847 hom., cov: 30)
• Consequence: GOSR2 NM_004287.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOSR2	NM_004287.5	c.30-1056G>A		intron_variant	Intron 1 of 5	ENST00000640051.2	NP_004278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2	c.30-1056G>A		intron_variant	Intron 1 of 5	1	NM_004287.5	ENSP00000492751.1
ENSG00000262633	ENST00000571841.1	n.30-1056G>A		intron_variant	Intron 1 of 9	5		ENSP00000461460.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68486 AN: 151724 Hom.: 15824 Cov.: 30

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.451 AC: 68551 AN: 151842 Hom.: 15847 Cov.: 30 AF XY: 0.450 AC XY: 33363 AN XY: 74218

African (AFR) AF: 0.365 AC: 15091 AN: 41372

American (AMR) AF: 0.417 AC: 6362 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3466

East Asian (EAS) AF: 0.301 AC: 1552 AN: 5150

South Asian (SAS) AF: 0.453 AC: 2173 AN: 4796

European-Finnish (FIN) AF: 0.478 AC: 5042 AN: 10550

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34776 AN: 67932

Other (OTH) AF: 0.443 AC: 931 AN: 2102

Alfa AF: 0.482 Hom.: 4453

Bravo AF: 0.440

Asia WGS AF: 0.406 AC: 1412 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	7.4
DANN	Benign	0.72
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

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: rs3785889; hg19: chr17-45005830;