chr5-35203290-G-A

Variant names:

• chr5-35203290-G-A
• rs2047740
• NM_000949.7:c.-106+26978C>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.-106+26978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,040 control chromosomes in the GnomAD database, including 25,925 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 0.57 (25925 hom., cov: 33)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 8 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 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.-106+26978C>T		intron	N/A	NP_000940.1	P16471-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	ENST00000618457.5	TSL:1 MANE Select	c.-106+26978C>T		intron	N/A	ENSP00000482954.1	P16471-1
	PRLR	ENST00000852369.1		c.-44+26978C>T		intron	N/A	ENSP00000522428.1
	PRLR	ENST00000852370.1		c.-398-7577C>T		intron	N/A	ENSP00000522429.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86816 AN: 151922 Hom.: 25923 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.571 AC: 86843 AN: 152040 Hom.: 25925 Cov.: 33 AF XY: 0.570 AC XY: 42360 AN XY: 74314

African (AFR) AF: 0.422 AC: 17483 AN: 41476

American (AMR) AF: 0.547 AC: 8353 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1656 AN: 5180

South Asian (SAS) AF: 0.649 AC: 3127 AN: 4818

European-Finnish (FIN) AF: 0.612 AC: 6463 AN: 10560

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45532 AN: 67946

Other (OTH) AF: 0.570 AC: 1202 AN: 2110

Alfa AF: 0.630 Hom.: 21859

Bravo AF: 0.556

Asia WGS AF: 0.496 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.3
DANN	Benign	0.79
PhyloP100		0.029
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: rs2047740; hg19: chr5-35203392;