chr5-35221949-C-G

Variant names:

• chr5-35221949-C-G
• rs931741
• NM_000949.7:c.-106+8319G>C

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+8319G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,100 control chromosomes in the GnomAD database, including 27,885 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 0.59 (27885 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	NM_000949.7	MANE Select	c.-106+8319G>C		intron	N/A	NP_000940.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	ENST00000618457.5	TSL:1 MANE Select	c.-106+8319G>C		intron	N/A	ENSP00000482954.1
	PRLR	ENST00000504500.5	TSL:3	c.-293+8319G>C		intron	N/A	ENSP00000422867.1
	PRLR	ENST00000515839.1	TSL:2	c.-269+8319G>C		intron	N/A	ENSP00000421864.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89938 AN: 151982 Hom.: 27868 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.592 AC: 89985 AN: 152100 Hom.: 27885 Cov.: 32 AF XY: 0.590 AC XY: 43884 AN XY: 74358

African (AFR) AF: 0.429 AC: 17781 AN: 41484

American (AMR) AF: 0.591 AC: 9034 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2241 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1706 AN: 5168

South Asian (SAS) AF: 0.680 AC: 3280 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6528 AN: 10568

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47285 AN: 67992

Other (OTH) AF: 0.596 AC: 1261 AN: 2116

Alfa AF: 0.645 Hom.: 4025

Bravo AF: 0.577

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.36
PhyloP100		-0.23
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: rs931741; hg19: chr5-35222051;