5-35145261-T-C

Variant names:

• chr5-35145261-T-C
• rs9292571
• NM_000949.7:c.-105-27139A>G

Variant summary

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

The NM_000949.7(PRLR):​c.-105-27139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,092 control chromosomes in the GnomAD database, including 56,683 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 0.85 (56683 hom., cov: 31)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-105-27139A>G		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.-105-27139A>G		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129340 AN: 151974 Hom.: 56653 Cov.: 31

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.851 AC: 129418 AN: 152092 Hom.: 56683 Cov.: 31 AF XY: 0.853 AC XY: 63430 AN XY: 74364

African (AFR) AF: 0.619 AC: 25650 AN: 41428

American (AMR) AF: 0.921 AC: 14083 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3243 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4354 AN: 5170

South Asian (SAS) AF: 0.957 AC: 4603 AN: 4812

European-Finnish (FIN) AF: 0.947 AC: 10058 AN: 10618

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64454 AN: 67980

Other (OTH) AF: 0.862 AC: 1821 AN: 2112

Alfa AF: 0.918 Hom.: 265415

Bravo AF: 0.837

Asia WGS AF: 0.895 AC: 3112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.54
DANN	Benign	0.56
PhyloP100		-0.063
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: rs9292571; hg19: chr5-35145363;