dbSNP rs43215: PRLR:c.71-527G>A (chr5-35086867-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000949.7(PRLR):c.71-527G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,014 control chromosomes in the GnomAD database, including 4,257 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 4257 hom., cov: 31)

Consequence

PRLR
NM_000949.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

familial hyperprolactinemia
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

PRLR links:

ENSG00000301126 (HGNC:):

ENSG00000301126 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000949.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000949.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRLR	NM_000949.7	MANE Select	c.71-527G>A	intron	N/A	NP_000940.1	P16471-1
PRLR	NM_001204314.2		c.70+2684G>A	intron	N/A	NP_001191243.1	P16471-2
PRLR	NM_001204316.1		c.71-527G>A	intron	N/A	NP_001191245.1	P16471-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRLR	ENST00000618457.5	TSL:1 MANE Select	c.71-527G>A	intron	N/A	ENSP00000482954.1	P16471-1
PRLR	ENST00000511486.5	TSL:1	c.70+2684G>A	intron	N/A	ENSP00000422556.1	P16471-2
PRLR	ENST00000231423.7	TSL:1	c.71-527G>A	intron	N/A	ENSP00000231423.3	P16471-4

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30003

AN:

151896

Hom.:

4255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.198

AC:

30034

AN:

152014

Hom.:

4257

Cov.:

AF XY:

0.197

AC XY:

14672

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.403

AC:

16665

AN:

41386

American (AMR)

AF:

0.114

AC:

1747

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3470

East Asian (EAS)

AF:

0.264

AC:

1364

AN:

5168

South Asian (SAS)

AF:

0.183

AC:

882

AN:

4820

European-Finnish (FIN)

AF:

0.111

AC:

1177

AN:

10584

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7171

AN:

67980

Other (OTH)

AF:

0.189

AC:

400

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1093

2186

3280

4373

5466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.143

Hom.:

907

Bravo

AF:

0.205

Asia WGS

AF:

0.208

AC:

725

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

(source)

DANN

Benign

0.73

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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