rs249528

chr5-35099890-G-T

Variant summary

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

The NM_000949.7(PRLR):c.-43-10227C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,142 control chromosomes in the GnomAD database, including 556 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 0.056 (556 hom., cov: 31)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRLR	NM_000949.7	c.-43-10227C>A		intron_variant		ENST00000618457.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRLR	ENST00000618457.5	c.-43-10227C>A		intron_variant		1	NM_000949.7	P1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8483 AN: 152024 Hom.: 553 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.00972

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00977

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0559 AC: 8499 AN: 152142 Hom.: 556 Cov.: 31 AF XY: 0.0567 AC XY: 4222 AN XY: 74402

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.00972

Gnomad4 NFE AF: 0.00977

Gnomad4 OTH AF: 0.0484

Alfa AF: 0.0361 Hom.: 47

Bravo AF: 0.0631

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.75

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: rs249528; hg19: chr5-35099992;