rs62355518

Variant names:

• chr5-35182919-T-C
• rs62355518
• NM_000949.7:c.-106+47349A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000949.7(PRLR):​c.-106+47349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,212 control chromosomes in the GnomAD database, including 2,849 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 0.19 (2849 hom., cov: 33)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+47349A>G		intron_variant	Intron 1 of 9	ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-106+47349A>G		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28286 AN: 152094 Hom.: 2850 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.186 AC: 28295 AN: 152212 Hom.: 2849 Cov.: 33 AF XY: 0.183 AC XY: 13628 AN XY: 74428

African (AFR) AF: 0.264 AC: 10937 AN: 41490

American (AMR) AF: 0.164 AC: 2516 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3466

East Asian (EAS) AF: 0.149 AC: 774 AN: 5186

South Asian (SAS) AF: 0.0642 AC: 310 AN: 4830

European-Finnish (FIN) AF: 0.154 AC: 1634 AN: 10602

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10830 AN: 68022

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.177 Hom.: 300

Bravo AF: 0.194

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.94
DANN	Benign	0.74
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62355518; hg19: chr5-35183021;