NM_000949.7:c.-106+33000C>G

Variant names:

• chr5-35197268-G-C
• rs17249539
• NM_000949.7:c.-106+33000C>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.-106+33000C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,294 control chromosomes in the GnomAD database, including 963 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 0.099 (963 hom., cov: 33)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+33000C>G		intron_variant	Intron 1 of 9	ENST00000618457.5	NP_000940.1
PRLR	XM_024446131.2	c.59+33000C>G		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+33000C>G		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1
PRLR	ENST00000504500.5	c.-293+33000C>G		intron_variant	Intron 1 of 4	3		ENSP00000422867.1
PRLR	ENST00000515839.1	c.-268-1555C>G		intron_variant	Intron 1 of 4	2		ENSP00000421864.1
PRLR	ENST00000508107.5	n.-106+33000C>G		intron_variant	Intron 1 of 6	3		ENSP00000427236.1

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15047 AN: 152176 Hom.: 960 Cov.: 33

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0989 AC: 15055 AN: 152294 Hom.: 963 Cov.: 33 AF XY: 0.100 AC XY: 7471 AN XY: 74480

African (AFR) AF: 0.0344 AC: 1429 AN: 41572

American (AMR) AF: 0.122 AC: 1873 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.0152 AC: 79 AN: 5186

South Asian (SAS) AF: 0.122 AC: 590 AN: 4828

European-Finnish (FIN) AF: 0.166 AC: 1758 AN: 10618

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8589 AN: 68002

Other (OTH) AF: 0.105 AC: 222 AN: 2116

Alfa AF: 0.103 Hom.: 120

Bravo AF: 0.0911

Asia WGS AF: 0.0990 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.82
DANN	Benign	0.32
PhyloP100		-0.26
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: rs17249539; hg19: chr5-35197370;