rs13436213

Variant names:

• chr5-35185724-C-T
• rs13436213
• NM_000949.7:c.-106+44544G>A

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+44544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,104 control chromosomes in the GnomAD database, including 8,026 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 (8026 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+44544G>A		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+44544G>A		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47150 AN: 151986 Hom.: 8029 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.310 AC: 47144 AN: 152104 Hom.: 8026 Cov.: 32 AF XY: 0.312 AC XY: 23173 AN XY: 74342

African (AFR) AF: 0.182 AC: 7545 AN: 41500

American (AMR) AF: 0.306 AC: 4675 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3466

East Asian (EAS) AF: 0.194 AC: 1008 AN: 5184

South Asian (SAS) AF: 0.396 AC: 1909 AN: 4816

European-Finnish (FIN) AF: 0.365 AC: 3858 AN: 10562

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25741 AN: 67976

Other (OTH) AF: 0.330 AC: 695 AN: 2104

Alfa AF: 0.352 Hom.: 31117

Bravo AF: 0.298

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.50
PhyloP100		0.011
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: rs13436213; hg19: chr5-35185826;