Variant rs291102 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002644.4(PIGR):c.1739C>T(p.Ala580Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 1,613,980 control chromosomes in the GnomAD database, including 20,518 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.22 ( 9736 hom., cov: 32)

Exomes 𝑓: 0.052 ( 10782 hom. )

Consequence

PIGR
NM_002644.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.533

Variant links:

Genes affected

PIGR (HGNC:8968): (polymeric immunoglobulin receptor) This gene is a member of the immunoglobulin superfamily. The encoded poly-Ig receptor binds polymeric immunoglobulin molecules at the basolateral surface of epithelial cells; the complex is then transported across the cell to be secreted at the apical surface. A significant association was found between immunoglobulin A nephropathy and several SNPs in this gene.[provided by RefSeq, Sep 2009]

PIGR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.5720843E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGR	NM_002644.4 linkuse as main transcript	c.1739C>T	p.Ala580Val	missense_variant	7/11	ENST00000356495.5	NP_002635.2
PIGR	XM_011509629.2 linkuse as main transcript	c.1739C>T	p.Ala580Val	missense_variant	7/11		XP_011507931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGR	ENST00000356495.5 linkuse as main transcript	c.1739C>T	p.Ala580Val	missense_variant	7/11	1	NM_002644.4	ENSP00000348888	P1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33813

AN:

152078

Hom.:

9693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.00395

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.104

AC:

26055

AN:

251408

Hom.:

4942

AF XY:

0.0852

AC XY:

11580

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.683

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.0958

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.0420

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0696

GnomAD4 exome

AF:

0.0525

AC:

76729

AN:

1461784

Hom.:

10782

Cov.:

AF XY:

0.0495

AC XY:

36026

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.695

Gnomad4 AMR exome

AF:

0.207

Gnomad4 ASJ exome

AF:

0.0924

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.0427

Gnomad4 FIN exome

AF:

0.00474

Gnomad4 NFE exome

AF:

0.0241

Gnomad4 OTH exome

AF:

0.0836

GnomAD4 genome

AF:

0.223

AC:

33916

AN:

152196

Hom.:

9736

Cov.:

AF XY:

0.219

AC XY:

16321

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.666

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.0971

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0449

Gnomad4 FIN

AF:

0.00395

Gnomad4 NFE

AF:

0.0254

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.0586

Hom.:

3456

Bravo

AF:

0.257

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0270

AC:

104

ESP6500AA

AF:

0.656

AC:

2890

ESP6500EA

AF:

0.0293

AC:

252

ExAC

AF:

0.109

AC:

13207

Asia WGS

AF:

0.120

AC:

416

AN:

3478

EpiCase

AF:

0.0244

EpiControl

AF:

0.0258

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IgA glomerulonephritis

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.8

DANN

Benign

0.91

DEOGEN2

Benign

0.14

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0000036

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.64

REVEL

Benign

0.019

Sift

Benign

0.68

Sift4G

Benign

0.24

Polyphen

0.0080

Vest4

0.040

MPC

0.32

ClinPred

0.00030

GERP RS

1.1

Varity_R

0.024

gMVP

0.15

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over