5-35072278-T-G

Variant names:

• chr5-35072278-T-G
• rs37364
• NM_000949.7:c.543+297A>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.543+297A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,052 control chromosomes in the GnomAD database, including 12,315 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 0.34 (12315 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• 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

ENSG00000301126 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.543+297A>C		intron_variant	Intron 6 of 9	ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.543+297A>C		intron_variant	Intron 6 of 9	1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51021 AN: 151934 Hom.: 12273 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.0408

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.336 AC: 51111 AN: 152052 Hom.: 12315 Cov.: 32 AF XY: 0.330 AC XY: 24562 AN XY: 74346

African (AFR) AF: 0.682 AC: 28254 AN: 41440

American (AMR) AF: 0.220 AC: 3354 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3466

East Asian (EAS) AF: 0.289 AC: 1494 AN: 5174

South Asian (SAS) AF: 0.282 AC: 1360 AN: 4828

European-Finnish (FIN) AF: 0.138 AC: 1459 AN: 10588

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13547 AN: 67982

Other (OTH) AF: 0.315 AC: 664 AN: 2106

Alfa AF: 0.253 Hom.: 8294

Bravo AF: 0.354

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.63
PhyloP100		-0.13
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: rs37364; hg19: chr5-35072380;