17-46923121-A-G

Variant names:

• chr17-46923121-A-G
• rs1598902094
• ENST00000225567.9:c.-72A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000225567.9(GOSR2):​c.-72A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 940,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GOSR2 ENST00000225567.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• 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]

GOSR2-DT (HGNC:55346): (GOSR2 divergent transcript)

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]

ENSG00000262633 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000225567.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	NM_004287.5	MANE Select	c.-72A>G		upstream_gene	N/A	NP_004278.2
	GOSR2	NM_001321133.2		c.-72A>G		upstream_gene	N/A	NP_001308062.1
	GOSR2	NM_054022.4		c.-72A>G		upstream_gene	N/A	NP_473363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000225567.9	TSL:1	c.-72A>G		5_prime_UTR	Exon 1 of 7	ENSP00000225567.4
	GOSR2	ENST00000640358.1	TSL:5	n.-72A>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000491135.1
	GOSR2	ENST00000640792.1	TSL:5	n.-72A>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000492736.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000213 AC: 2 AN: 940466 Hom.: 0 Cov.: 13 AF XY: 0.00000416 AC XY: 2 AN XY: 481292

African (AFR) AF: 0.00 AC: 0 AN: 23428

American (AMR) AF: 0.00 AC: 0 AN: 35134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22218

East Asian (EAS) AF: 0.0000297 AC: 1 AN: 33708

South Asian (SAS) AF: 0.0000143 AC: 1 AN: 70138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 662958

Other (OTH) AF: 0.00 AC: 0 AN: 42920

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.12
PromoterAI		-0.092	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1598902094; hg19: chr17-45000487;