rs7734558

Variant names:

• chr5-35114509-G-A
• rs7734558
• NM_000949.7:c.-44+3552C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-35114509-G-A
• chr5-35114509-G-C
• chr5-35114509-G-T

Variant summary

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

The NM_000949.7(PRLR):​c.-44+3552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,076 control chromosomes in the GnomAD database, including 14,281 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 0.39 (14281 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862
• Publications: 10 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

ENSG00000301126 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-44+3552C>T		intron_variant	Intron 2 of 9	ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-44+3552C>T		intron_variant	Intron 2 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59353 AN: 151958 Hom.: 14280 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.390 AC: 59339 AN: 152076 Hom.: 14281 Cov.: 32 AF XY: 0.386 AC XY: 28657 AN XY: 74334

African (AFR) AF: 0.141 AC: 5840 AN: 41512

American (AMR) AF: 0.350 AC: 5335 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1667 AN: 3466

East Asian (EAS) AF: 0.0542 AC: 280 AN: 5166

South Asian (SAS) AF: 0.430 AC: 2073 AN: 4818

European-Finnish (FIN) AF: 0.484 AC: 5118 AN: 10566

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37519 AN: 67972

Other (OTH) AF: 0.414 AC: 874 AN: 2112

Alfa AF: 0.493 Hom.: 61385

Bravo AF: 0.367

Asia WGS AF: 0.265 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.30
PhyloP100		-0.86
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: rs7734558; hg19: chr5-35114611;