dbSNP rs4425481: PRLR:c.-106+44473G>T (chr5-35185795-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000949.7(PRLR):c.-106+44473G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 152,214 control chromosomes in the GnomAD database, including 214 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 0.049 ( 214 hom., cov: 32)

Consequence

PRLR
NM_000949.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.276

Publications

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

PRLR links:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0687 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	NM_000949.7	MANE Select	c.-106+44473G>T		intron	N/A	NP_000940.1	P16471-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRLR	ENST00000618457.5	TSL:1 MANE Select	c.-106+44473G>T	intron	N/A	ENSP00000482954.1	P16471-1
PRLR	ENST00000509839.5	TSL:1	c.-106+9308G>T	intron	N/A	ENSP00000427060.1	D6RD41
PRLR	ENST00000852369.1		c.-44+44473G>T	intron	N/A	ENSP00000522428.1

Frequencies

GnomAD3 genomes

AF:

0.0487

AC:

7403

AN:

152096

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.0735

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.0342

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0677

Gnomad OTH

AF:

0.0631

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

GnomAD4 genome

AF:

0.0486

AC:

7396

AN:

152214

Hom.:

214

Cov.:

AF XY:

0.0473

AC XY:

3518

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0156

AC:

650

AN:

41534

American (AMR)

AF:

0.0722

AC:

1105

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0735

AC:

255

AN:

3470

East Asian (EAS)

AF:

0.0272

AC:

141

AN:

5186

South Asian (SAS)

AF:

0.0349

AC:

168

AN:

4816

European-Finnish (FIN)

AF:

0.0238

AC:

252

AN:

10598

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0677

AC:

4604

AN:

67988

Other (OTH)

AF:

0.0615

AC:

130

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

364

729

1093

1458

1822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0596

Hom.:

537

Bravo

AF:

0.0521

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.2

(source)

DANN

Benign

0.52

PhyloP100

0.28

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