rs291102

chr1-206933133-G-Achr1-206933133-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/19 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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.533

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]

ACMG classification

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	UniProt
PIGR	NM_002644.4	c.1739C>T	p.Ala580Val	missense_variant	7/11	ENST00000356495.5
PIGR	XM_011509629.2	c.1739C>T	p.Ala580Val	missense_variant	7/11

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33813 AN: 152078 Hom.: 9693 Cov.: 32

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

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.: 32 AF XY: 0.0495 AC XY: 36026 AN XY: 727192

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.: 32 AF XY: 0.219 AC XY: 16321 AN XY: 74426

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: 96

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

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	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.8
Dann	Benign	0.91
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0000036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.019
Sift	Benign	0.68	T
Sift4G	Benign	0.24	T
Polyphen		0.0080	B
Vest4		0.040
MPC		0.32
ClinPred		0.00030	T
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

Other links and lift over

dbSNP: rs291102; hg19: chr1-207106478; COSMIC: COSV62903533; COSMIC: COSV62903533;