NM_000949.7:c.-105-53797C>T

Variant names:

• chr5-35171919-G-A
• rs4703505
• NM_000949.7:c.-105-53797C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000949.7(PRLR):​c.-105-53797C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,968 control chromosomes in the GnomAD database, including 7,477 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 (7477 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) 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.-105-53797C>T		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.-105-53797C>T		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46699 AN: 151848 Hom.: 7458 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.308 AC: 46766 AN: 151968 Hom.: 7477 Cov.: 32 AF XY: 0.305 AC XY: 22688 AN XY: 74278

African (AFR) AF: 0.387 AC: 16040 AN: 41402

American (AMR) AF: 0.288 AC: 4396 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3468

East Asian (EAS) AF: 0.165 AC: 852 AN: 5162

South Asian (SAS) AF: 0.165 AC: 793 AN: 4812

European-Finnish (FIN) AF: 0.320 AC: 3376 AN: 10560

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19244 AN: 67956

Other (OTH) AF: 0.322 AC: 681 AN: 2116

Alfa AF: 0.170 Hom.: 414

Bravo AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.4
DANN	Benign	0.19
PhyloP100		0.38
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: rs4703505; hg19: chr5-35172021;