rs291102

Variant names:

• chr1-206933133-G-A
• rs291102
• NM_002644.4:c.1739C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-206933133-G-A
• chr1-206933133-G-C

Variant summary

Our verdict is Benign. The variant received -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. 15/22 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PIGR	NM_002644.4	c.1739C>T	p.Ala580Val	missense_variant	Exon 7 of 11	ENST00000356495.5	NP_002635.2
PIGR	XM_011509629.2	c.1739C>T	p.Ala580Val	missense_variant	Exon 7 of 11		XP_011507931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGR	ENST00000356495.5	c.1739C>T	p.Ala580Val	missense_variant	Exon 7 of 11	1	NM_002644.4	ENSP00000348888.4

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

GnomAD2 exomes AF: 0.104 AC: 26055 AN: 251408 AF XY: 0.0852

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 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 AC: 23271 AN: 33466

Gnomad4 AMR exome AF: 0.207 AC: 9249 AN: 44718

Gnomad4 ASJ exome AF: 0.0924 AC: 2415 AN: 26134

Gnomad4 EAS exome AF: 0.142 AC: 5634 AN: 39700

Gnomad4 SAS exome AF: 0.0427 AC: 3684 AN: 86250

Gnomad4 FIN exome AF: 0.00474 AC: 253 AN: 53404

Gnomad4 NFE exome AF: 0.0241 AC: 26773 AN: 1111960

Gnomad4 Remaining exome AF: 0.0836 AC: 5046 AN: 60384

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 AC: 0.666072 AN: 0.666072

Gnomad4 AMR AF: 0.196 AC: 0.195908 AN: 0.195908

Gnomad4 ASJ AF: 0.0971 AC: 0.0970622 AN: 0.0970622

Gnomad4 EAS AF: 0.110 AC: 0.109954 AN: 0.109954

Gnomad4 SAS AF: 0.0449 AC: 0.0449461 AN: 0.0449461

Gnomad4 FIN AF: 0.00395 AC: 0.00395406 AN: 0.00395406

Gnomad4 NFE AF: 0.0254 AC: 0.0254499 AN: 0.0254499

Gnomad4 OTH AF: 0.181 AC: 0.181345 AN: 0.181345

Alfa AF: 0.0815 Hom.: 11281

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

Jan 01, 2006

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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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
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
Mutation Taster		=99/1	polymorphism (auto)

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;