chr5-35114509-G-A

Position:

• chr5-35114509-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-44+3552C>T		intron_variant		ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-44+3552C>T		intron_variant		1	NM_000949.7	ENSP00000482954	P1

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.414

Alfa AF: 0.519 Hom.: 41240

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7734558; hg19: chr5-35114611;