dbSNP rs781672177: PIGR:p.Val753Leu (chr1-206930356-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002644.4(PIGR):c.2257G>T(p.Val753Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V753M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIGR
NM_002644.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.757

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03839934).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002644.4. 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
	PIGR	NM_002644.4	MANE Select	c.2257G>T	p.Val753Leu	missense	Exon 11 of 11	NP_002635.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIGR	ENST00000356495.5	TSL:1 MANE Select	c.2257G>T	p.Val753Leu	missense	Exon 11 of 11	ENSP00000348888.4	P01833
PIGR	ENST00000942167.1		c.2317G>T	p.Val773Leu	missense	Exon 11 of 11	ENSP00000612226.1
PIGR	ENST00000860528.1		c.2278G>T	p.Val760Leu	missense	Exon 11 of 11	ENSP00000530587.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246244

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459398

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726082

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

44478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39396

South Asian (SAS)

AF:

0.00

AC:

AN:

85934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110770

Other (OTH)

AF:

0.00

AC:

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.3

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.12

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.42

M_CAP

Benign

0.0093

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

0.76

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.24

REVEL

Benign

0.045

Sift

Benign

0.25

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.023

MutPred

0.089

Gain of helix (P = 0.132)

MVP

0.082

MPC

0.30

ClinPred

0.50

GERP RS

1.7

Varity_R

0.030

gMVP

0.027

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over