rs2047740

chr5-35203290-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000949.7(PRLR):c.-106+26978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,040 control chromosomes in the GnomAD database, including 25,925 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 0.57 (25925 hom., cov: 33)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRLR	NM_000949.7	c.-106+26978C>T		intron_variant		ENST00000618457.5
PRLR	XM_024446131.2	c.59+26978C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRLR	ENST00000618457.5	c.-106+26978C>T		intron_variant		1	NM_000949.7	P1
PRLR	ENST00000504500.5	c.-293+26978C>T		intron_variant		3
PRLR	ENST00000515839.1	c.-268-7577C>T		intron_variant		2
PRLR	ENST00000508107.5	c.-106+26978C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86816 AN: 151922 Hom.: 25923 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.571 AC: 86843 AN: 152040 Hom.: 25925 Cov.: 33 AF XY: 0.570 AC XY: 42360 AN XY: 74314

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.570

Alfa AF: 0.643 Hom.: 15580

Bravo AF: 0.556

Asia WGS AF: 0.496 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	4.3
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs2047740; hg19: chr5-35203392;