5-35060217-C-T

Position:

• chr5-35060217-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.*4872G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,038 control chromosomes in the GnomAD database, including 4,216 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 0.20 (4216 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRLR NM_000949.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRLR	NM_000949.7	c.*4872G>A		3_prime_UTR_variant	10/10	ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457	c.*4872G>A		3_prime_UTR_variant	10/10	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30390 AN: 151920 Hom.: 4210 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0638

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.190

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.200 AC: 30432 AN: 152038 Hom.: 4216 Cov.: 32 AF XY: 0.194 AC XY: 14423 AN XY: 74344

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0638

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.195

Alfa AF: 0.134 Hom.: 975

Bravo AF: 0.216

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.72

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: rs249522; hg19: chr5-35060319;