rs7718468

Variant names:

• chr5-35200934-A-G
• rs7718468
• NM_000949.7:c.-106+29334T>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+29334T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,094 control chromosomes in the GnomAD database, including 6,992 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 0.28 (6992 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+29334T>C		intron_variant	Intron 1 of 9	ENST00000618457.5	NP_000940.1
PRLR	XM_024446131.2	c.59+29334T>C		intron_variant	Intron 1 of 8		XP_024301899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-106+29334T>C		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1
PRLR	ENST00000504500.5	c.-293+29334T>C		intron_variant	Intron 1 of 4	3		ENSP00000422867.1
PRLR	ENST00000515839.1	c.-268-5221T>C		intron_variant	Intron 1 of 4	2		ENSP00000421864.1
PRLR	ENST00000508107.5	n.-106+29334T>C		intron_variant	Intron 1 of 6	3		ENSP00000427236.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41862 AN: 151978 Hom.: 6988 Cov.: 32

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.275 AC: 41856 AN: 152094 Hom.: 6992 Cov.: 32 AF XY: 0.277 AC XY: 20580 AN XY: 74350

African (AFR) AF: 0.0996 AC: 4139 AN: 41542

American (AMR) AF: 0.297 AC: 4537 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1306 AN: 3470

East Asian (EAS) AF: 0.0713 AC: 369 AN: 5178

South Asian (SAS) AF: 0.394 AC: 1896 AN: 4818

European-Finnish (FIN) AF: 0.340 AC: 3590 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24961 AN: 67938

Other (OTH) AF: 0.306 AC: 647 AN: 2114

Alfa AF: 0.347 Hom.: 8128

Bravo AF: 0.259

Asia WGS AF: 0.263 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.73
PhyloP100		0.16
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: rs7718468; hg19: chr5-35201036;