Variant 1-206935771-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002644.4(PIGR):c.1093G>A(p.Gly365Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,611,080 control chromosomes in the GnomAD database, including 146,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 11025 hom., cov: 31)

Exomes 𝑓: 0.43 ( 135766 hom. )

Consequence

PIGR
NM_002644.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.462

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001230061).

BP6

Variant 1-206935771-C-T is Benign according to our data. Variant chr1-206935771-C-T is described in ClinVar as [Benign]. Clinvar id is 1283436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 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.1093G>A	p.Gly365Ser	missense_variant	5/11	ENST00000356495.5	NP_002635.2	P01833
PIGR	XM_011509629.2 linkuse as main transcript	c.1093G>A	p.Gly365Ser	missense_variant	5/11		XP_011507931.1	P01833

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGR	ENST00000356495.5 linkuse as main transcript	c.1093G>A	p.Gly365Ser	missense_variant	5/11	1	NM_002644.4	ENSP00000348888.4		P01833

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55593

AN:

151990

Hom.:

11020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.414

GnomAD3 exomes

AF:

0.381

AC:

94271

AN:

247152

Hom.:

19138

AF XY:

0.384

AC XY:

51505

AN XY:

133986

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.474

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.425

AC:

620116

AN:

1458972

Hom.:

135766

Cov.:

AF XY:

0.422

AC XY:

306239

AN XY:

725364

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.413

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.366

AC:

55620

AN:

152108

Hom.:

11025

Cov.:

AF XY:

0.359

AC XY:

26683

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.444

Hom.:

24542

Bravo

AF:

0.357

TwinsUK

AF:

0.449

AC:

1664

ALSPAC

AF:

0.440

AC:

1695

ESP6500AA

AF:

0.219

AC:

963

ESP6500EA

AF:

0.458

AC:

3938

ExAC

AF:

0.379

AC:

46022

Asia WGS

AF:

0.281

AC:

976

AN:

3478

EpiCase

AF:

0.467

EpiControl

AF:

0.464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.13

Sift

Benign

0.12

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.038

MPC

0.93

ClinPred

0.036

GERP RS

4.6

Varity_R

0.46

gMVP

0.88

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