rs4703509

Variant names:

• chr5-35200092-T-C
• rs4703509
• NM_000949.7:c.-106+30176A>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+30176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,080 control chromosomes in the GnomAD database, including 8,015 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 0.31 (8015 hom., cov: 33)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+30176A>G		intron_variant	Intron 1 of 9	ENST00000618457.5	NP_000940.1
PRLR	XM_024446131.2	c.59+30176A>G		intron_variant	Intron 1 of 8		XP_024301899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-106+30176A>G		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1
PRLR	ENST00000504500.5	c.-293+30176A>G		intron_variant	Intron 1 of 4	3		ENSP00000422867.1
PRLR	ENST00000515839.1	c.-268-4379A>G		intron_variant	Intron 1 of 4	2		ENSP00000421864.1
PRLR	ENST00000508107.5	n.-106+30176A>G		intron_variant	Intron 1 of 6	3		ENSP00000427236.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46609 AN: 151962 Hom.: 7991 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.307 AC: 46676 AN: 152080 Hom.: 8015 Cov.: 33 AF XY: 0.303 AC XY: 22493 AN XY: 74336

African (AFR) AF: 0.461 AC: 19118 AN: 41468

American (AMR) AF: 0.260 AC: 3978 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3472

East Asian (EAS) AF: 0.133 AC: 686 AN: 5176

South Asian (SAS) AF: 0.163 AC: 783 AN: 4814

European-Finnish (FIN) AF: 0.311 AC: 3295 AN: 10582

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16974 AN: 67974

Other (OTH) AF: 0.304 AC: 641 AN: 2112

Alfa AF: 0.263 Hom.: 9466

Bravo AF: 0.312

Asia WGS AF: 0.181 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.2
DANN	Benign	0.43
PhyloP100		0.073
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: rs4703509; hg19: chr5-35200194;