NM_000949.7:c.71-527G>A

Variant names:

• chr5-35086867-C-T
• rs43215
• NM_000949.7:c.71-527G>A

Variant summary

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

The NM_000949.7(PRLR):​c.71-527G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,014 control chromosomes in the GnomAD database, including 4,257 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 (4257 hom., cov: 31)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.71-527G>A		intron_variant	Intron 3 of 9	ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.71-527G>A		intron_variant	Intron 3 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30003 AN: 151896 Hom.: 4255 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.198 AC: 30034 AN: 152014 Hom.: 4257 Cov.: 31 AF XY: 0.197 AC XY: 14672 AN XY: 74328

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.189

Alfa AF: 0.142 Hom.: 756

Bravo AF: 0.205

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.73

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: rs43215; hg19: chr5-35086969; COSMIC: COSV51500381; COSMIC: COSV51500381;