Variant chr5-35084545-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000949.7(PRLR):c.298A>G(p.Ile100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,606,348 control chromosomes in the GnomAD database, including 1,841 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.060 ( 456 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1385 hom. )

Consequence

PRLR
NM_000949.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0210

Variant links:

Genes affected

PRLR (HGNC:9446): (prolactin receptor) This gene encodes a receptor for the anterior pituitary hormone, prolactin, and belongs to the type I cytokine receptor family. Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor. Several alternatively spliced transcript variants encoding different membrane-bound and soluble isoforms have been described for this gene, which may function to modulate the endocrine and autocrine effects of prolactin in normal tissue and cancer. [provided by RefSeq, Feb 2011]

PRLR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022225678).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRLR	NM_000949.7 linkuse as main transcript	c.298A>G	p.Ile100Val	missense_variant	5/10	ENST00000618457.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRLR	ENST00000618457.5 linkuse as main transcript	c.298A>G	p.Ile100Val	missense_variant	5/10	1	NM_000949.7	P1	P16471-1

Frequencies

GnomAD3 genomes

AF:

0.0602

AC:

9155

AN:

152174

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0509

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0293

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0406

AC:

9860

AN:

242978

Hom.:

354

AF XY:

0.0417

AC XY:

5479

AN XY:

131354

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.0256

Gnomad ASJ exome

AF:

0.0411

Gnomad EAS exome

AF:

0.0310

Gnomad SAS exome

AF:

0.0872

Gnomad FIN exome

AF:

0.00501

Gnomad NFE exome

AF:

0.0286

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0352

AC:

51209

AN:

1454056

Hom.:

1385

Cov.:

AF XY:

0.0368

AC XY:

26617

AN XY:

723040

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0288

Gnomad4 ASJ exome

AF:

0.0424

Gnomad4 EAS exome

AF:

0.0333

Gnomad4 SAS exome

AF:

0.0858

Gnomad4 FIN exome

AF:

0.00549

Gnomad4 NFE exome

AF:

0.0292

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0602

AC:

9171

AN:

152292

Hom.:

456

Cov.:

AF XY:

0.0595

AC XY:

4434

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0508

Gnomad4 ASJ

AF:

0.0484

Gnomad4 EAS

AF:

0.0350

Gnomad4 SAS

AF:

0.0891

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.0293

Gnomad4 OTH

AF:

0.0549

Alfa

AF:

0.0381

Hom.:

245

Bravo

AF:

0.0662

TwinsUK

AF:

0.0262

AC:

ALSPAC

AF:

0.0288

AC:

111

ESP6500AA

AF:

0.124

AC:

548

ESP6500EA

AF:

0.0291

AC:

250

ExAC

AF:

0.0434

AC:

5274

Asia WGS

AF:

0.0530

AC:

183

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.0010

DANN

Benign

0.42

DEOGEN2

Benign

0.26

.;.;.;.;.;.;T;.;.;T;.;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.47

.;.;T;T;T;.;T;.;T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.53

N;N;N;N;N;N;N;N;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.14

N;N;.;N;.;N;.;N;.;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.51

T;T;.;T;.;T;.;T;.;T;T;T

Sift4G

Benign

0.51

T;T;T;T;T;T;T;T;T;.;.;.

Polyphen

0.0

B;B;B;B;B;B;B;.;.;.;.;.

Vest4

0.0070

ClinPred

0.0020

GERP RS

3.4

Varity_R

0.072

gMVP

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over