NM_000949.7:c.-106+44473G>T

Variant names:

• chr5-35185795-C-A
• rs4425481
• NM_000949.7:c.-106+44473G>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.-106+44473G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 152,214 control chromosomes in the GnomAD database, including 214 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 0.049 (214 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 5 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 (AMR) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+44473G>T		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+44473G>T		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7403 AN: 152096 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.0631

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

GnomAD4 genome AF: 0.0486 AC: 7396 AN: 152214 Hom.: 214 Cov.: 32 AF XY: 0.0473 AC XY: 3518 AN XY: 74424

African (AFR) AF: 0.0156 AC: 650 AN: 41534

American (AMR) AF: 0.0722 AC: 1105 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 255 AN: 3470

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5186

South Asian (SAS) AF: 0.0349 AC: 168 AN: 4816

European-Finnish (FIN) AF: 0.0238 AC: 252 AN: 10598

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0677 AC: 4604 AN: 67988

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0596 Hom.: 537

Bravo AF: 0.0521

Asia WGS AF: 0.0350 AC: 120 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	5.2
DANN	Benign	0.52
PhyloP100		0.28
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: rs4425481; hg19: chr5-35185897;