NM_000949.7:c.-43-9355C>T

Variant names:

• chr5-35099018-G-A
• rs35614689
• NM_000949.7:c.-43-9355C>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.-43-9355C>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 151,926 control chromosomes in the GnomAD database, including 14,230 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 (14230 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 2 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: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000301126 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000949.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	NM_000949.7	MANE Select	c.-43-9355C>T		intron	N/A	NP_000940.1	P16471-1
	PRLR	NM_001204314.2		c.-43-9355C>T		intron	N/A	NP_001191243.1	P16471-2
	PRLR	NM_001204316.1		c.-43-9355C>T		intron	N/A	NP_001191245.1	P16471-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	ENST00000618457.5	TSL:1 MANE Select	c.-43-9355C>T		intron	N/A	ENSP00000482954.1	P16471-1
	PRLR	ENST00000509839.5	TSL:1	c.-43-9355C>T		intron	N/A	ENSP00000427060.1	D6RD41
	PRLR	ENST00000852369.1		c.-43-9355C>T		intron	N/A	ENSP00000522428.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59213 AN: 151808 Hom.: 14229 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.390 AC: 59200 AN: 151926 Hom.: 14230 Cov.: 32 AF XY: 0.385 AC XY: 28580 AN XY: 74266

African (AFR) AF: 0.141 AC: 5830 AN: 41420

American (AMR) AF: 0.350 AC: 5348 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1669 AN: 3462

East Asian (EAS) AF: 0.0509 AC: 262 AN: 5146

South Asian (SAS) AF: 0.421 AC: 2027 AN: 4818

European-Finnish (FIN) AF: 0.485 AC: 5110 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37447 AN: 67956

Other (OTH) AF: 0.413 AC: 874 AN: 2116

Alfa AF: 0.436 Hom.: 5751

Bravo AF: 0.366

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.35
PhyloP100		0.20
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: rs35614689; hg19: chr5-35099120;