Genetic Variant PRLR:c.-106+30176A>G (chr5-35200092-T-C) – 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.-106+30176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,080 control chromosomes in the GnomAD database, including 8,015 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 0.31 ( 8015 hom., cov: 33)

Consequence

PRLR
NM_000949.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

10 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:

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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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7 link	c.-106+30176A>G		intron_variant	Intron 1 of 9	ENST00000618457.5	NP_000940.1	P16471-1
PRLR	XM_024446131.2 link	c.59+30176A>G		intron_variant	Intron 1 of 8		XP_024301899.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRLR	ENST00000618457.5 link	c.-106+30176A>G	intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1	P16471-1
PRLR	ENST00000504500.5 link	c.-293+30176A>G	intron_variant	Intron 1 of 4	3		ENSP00000422867.1	D6R9V7
PRLR	ENST00000515839.1 link	c.-268-4379A>G	intron_variant	Intron 1 of 4	2		ENSP00000421864.1	D6RAN9
PRLR	ENST00000508107.5 link	n.-106+30176A>G	intron_variant	Intron 1 of 6	3		ENSP00000427236.1	D6RJC8

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46609

AN:

151962

Hom.:

7991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.308

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

GnomAD4 genome

AF:

0.307

AC:

46676

AN:

152080

Hom.:

8015

Cov.:

AF XY:

0.303

AC XY:

22493

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.461

AC:

19118

AN:

41468

American (AMR)

AF:

0.260

AC:

3978

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

872

AN:

3472

East Asian (EAS)

AF:

0.133

AC:

686

AN:

5176

South Asian (SAS)

AF:

0.163

AC:

783

AN:

4814

European-Finnish (FIN)

AF:

0.311

AC:

3295

AN:

10582

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16974

AN:

67974

Other (OTH)

AF:

0.304

AC:

641

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1583

3166

4749

6332

7915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.263

Hom.:

9466

Bravo

AF:

0.312

Asia WGS

AF:

0.181

AC:

634

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

5.2

(source)

DANN

Benign

0.43

PhyloP100

0.073

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over