rs931741

Positions:

• chr5-35221949-C-G

Variant summary

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

The NM_000949.7(PRLR):​c.-106+8319G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,100 control chromosomes in the GnomAD database, including 27,885 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 0.59 (27885 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+8319G>C		intron_variant		ENST00000618457.5	NP_000940.1
PRLR	XM_024446131.2	c.59+8319G>C		intron_variant			XP_024301899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-106+8319G>C		intron_variant		1	NM_000949.7	ENSP00000482954	P1
PRLR	ENST00000504500.5	c.-293+8319G>C		intron_variant		3		ENSP00000422867
PRLR	ENST00000515839.1	c.-269+8319G>C		intron_variant		2		ENSP00000421864
PRLR	ENST00000508107.5	c.-106+8319G>C		intron_variant, NMD_transcript_variant		3		ENSP00000427236

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89938 AN: 151982 Hom.: 27868 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.592 AC: 89985 AN: 152100 Hom.: 27885 Cov.: 32 AF XY: 0.590 AC XY: 43884 AN XY: 74358

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.596

Alfa AF: 0.645 Hom.: 4025

Bravo AF: 0.577

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.36

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: rs931741; hg19: chr5-35222051;