16-20315999-G-A

Variant names:

• chr16-20315999-G-A
• rs115115341
• NM_001502.4:c.1458C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001502.4(GP2):​c.1458C>T​(p.Ile486Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,613,170 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (62 hom.)
• Consequence: GP2 NM_001502.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 16-20315999-G-A is Benign according to our data. Variant chr16-20315999-G-A is described in ClinVar as Benign. ClinVar VariationId is 717406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (2171/152216) while in subpopulation AFR AF = 0.0487 (2021/41516). AF 95% confidence interval is 0.0469. There are 40 homozygotes in GnomAd4. There are 1021 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 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.1458C>T	p.Ile486Ile	synonymous	Exon 9 of 11	NP_001493.2	P55259-3
	GP2	NM_001007240.3		c.1467C>T	p.Ile489Ile	synonymous	Exon 10 of 12	NP_001007241.2	P55259-1
	GP2	NM_001007241.3		c.1026C>T	p.Ile342Ile	synonymous	Exon 9 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.1458C>T	p.Ile486Ile	synonymous	Exon 9 of 11	ENSP00000304044.6	P55259-3
	GP2	ENST00000381362.8	TSL:1	c.1467C>T	p.Ile489Ile	synonymous	Exon 10 of 12	ENSP00000370767.4	P55259-1
	GP2	ENST00000381360.9	TSL:1	c.1026C>T	p.Ile342Ile	synonymous	Exon 9 of 11	ENSP00000370765.5	P55259-2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2169 AN: 152098 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00400 AC: 1006 AN: 251218 AF XY: 0.00290

Gnomad AFR exome AF: 0.0521

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000476

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00157 AC: 2296 AN: 1460954 Hom.: 62 Cov.: 29 AF XY: 0.00132 AC XY: 959 AN XY: 726876

African (AFR) AF: 0.0516 AC: 1725 AN: 33436

American (AMR) AF: 0.00291 AC: 130 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86236

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.000181 AC: 201 AN: 1111204

Other (OTH) AF: 0.00358 AC: 216 AN: 60356

GnomAD4 genome AF: 0.0143 AC: 2171 AN: 152216 Hom.: 40 Cov.: 32 AF XY: 0.0137 AC XY: 1021 AN XY: 74422

African (AFR) AF: 0.0487 AC: 2021 AN: 41516

American (AMR) AF: 0.00771 AC: 118 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68022

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00680 Hom.: 17

Bravo AF: 0.0164

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000178

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	-0.86
CADD	Benign	0.12
DANN	Benign	0.66
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.26		Position offset: 41

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

Other links and lift over

dbSNP: rs115115341; hg19: chr16-20327321;