rs76993218

Variant names:

• chr16-20311280-C-A
• rs76993218
• NM_001502.4:c.1548G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001502.4(GP2):​c.1548G>T​(p.Gly516Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,596,846 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (16 hom.)
• Consequence: GP2 NM_001502.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00001378
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.436
• Publications: 3 publications found

Genes affected

GP2 (HGNC:4441): (glycoprotein 2) This gene encodes an integral membrane protein that is secreted from intracellular zymogen granules and associates with the plasma membrane via glycosylphosphatidylinositol (GPI) linkage. The encoded protein binds pathogens such as enterobacteria, thereby playing an important role in the innate immune response. The C-terminus of this protein is related to the C-terminus of the protein encoded by the neighboring gene, uromodulin (UMOD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 16-20311280-C-A is Benign according to our data. Variant chr16-20311280-C-A is described in ClinVar as Benign. ClinVar VariationId is 786288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.436 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00808 (1231/152292) while in subpopulation AFR AF = 0.0273 (1133/41562). AF 95% confidence interval is 0.0259. There are 19 homozygotes in GnomAd4. There are 534 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001502.4. 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
	GP2	NM_001502.4	MANE Select	c.1548G>T	p.Gly516Gly	splice_region synonymous	Exon 11 of 11	NP_001493.2	P55259-3
	GP2	NM_001007240.3		c.1557G>T	p.Gly519Gly	splice_region synonymous	Exon 12 of 12	NP_001007241.2	P55259-1
	GP2	NM_001007241.3		c.1116G>T	p.Gly372Gly	splice_region synonymous	Exon 11 of 11	NP_001007242.2	P55259-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP2	ENST00000302555.10	TSL:1 MANE Select	c.1548G>T	p.Gly516Gly	splice_region synonymous	Exon 11 of 11	ENSP00000304044.6	P55259-3
	GP2	ENST00000381362.8	TSL:1	c.1557G>T	p.Gly519Gly	splice_region synonymous	Exon 12 of 12	ENSP00000370767.4	P55259-1
	GP2	ENST00000381360.9	TSL:1	c.1116G>T	p.Gly372Gly	splice_region synonymous	Exon 11 of 11	ENSP00000370765.5	P55259-2

Frequencies

GnomAD3 genomes AF: 0.00810 AC: 1232 AN: 152174 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00244 AC: 613 AN: 251040 AF XY: 0.00192

Gnomad AFR exome AF: 0.0279

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000894 AC: 1291 AN: 1444554 Hom.: 16 Cov.: 26 AF XY: 0.000826 AC XY: 595 AN XY: 720012

African (AFR) AF: 0.0251 AC: 830 AN: 33068

American (AMR) AF: 0.00351 AC: 157 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.0000931 AC: 8 AN: 85922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00384 AC: 22 AN: 5736

European-Non Finnish (NFE) AF: 0.000129 AC: 141 AN: 1096400

Other (OTH) AF: 0.00222 AC: 133 AN: 59776

GnomAD4 genome AF: 0.00808 AC: 1231 AN: 152292 Hom.: 19 Cov.: 32 AF XY: 0.00717 AC XY: 534 AN XY: 74454

African (AFR) AF: 0.0273 AC: 1133 AN: 41562

American (AMR) AF: 0.00431 AC: 66 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68026

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00341 Hom.: 14

Bravo AF: 0.00962

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.0
DANN	Benign	0.54
PhyloP100		-0.44
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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: rs76993218; hg19: chr16-20322602; COSMIC: COSV99043834;