5-35185478-C-T

Position:

• chr5-35185478-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000949.7(PRLR):​c.-106+44790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,578 control chromosomes in the GnomAD database, including 7,825 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 (7825 hom., cov: 31)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+44790G>A		intron_variant		ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-106+44790G>A		intron_variant		1	NM_000949.7	ENSP00000482954	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47514 AN: 151484 Hom.: 7805 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.314 AC: 47580 AN: 151578 Hom.: 7825 Cov.: 31 AF XY: 0.312 AC XY: 23063 AN XY: 74020

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.332

Alfa AF: 0.228 Hom.: 816

Bravo AF: 0.318

Asia WGS AF: 0.228 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.49

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: rs10941235; hg19: chr5-35185580;