NM_000949.7:c.-106+5223T>C

Variant names:

• chr5-35225045-A-G
• rs13354826
• NM_000949.7:c.-106+5223T>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+5223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,038 control chromosomes in the GnomAD database, including 7,130 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 (7130 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 2 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=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+5223T>C		intron_variant	Intron 1 of 9	ENST00000618457.5	NP_000940.1
PRLR	XM_024446131.2	c.59+5223T>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+5223T>C		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1
PRLR	ENST00000504500.5	c.-293+5223T>C		intron_variant	Intron 1 of 4	3		ENSP00000422867.1
PRLR	ENST00000515839.1	c.-269+5223T>C		intron_variant	Intron 1 of 4	2		ENSP00000421864.1
PRLR	ENST00000508107.5	n.-106+5223T>C		intron_variant	Intron 1 of 6	3		ENSP00000427236.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42455 AN: 151920 Hom.: 7122 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.279 AC: 42459 AN: 152038 Hom.: 7130 Cov.: 32 AF XY: 0.282 AC XY: 20984 AN XY: 74294

African (AFR) AF: 0.104 AC: 4323 AN: 41506

American (AMR) AF: 0.312 AC: 4765 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3470

East Asian (EAS) AF: 0.0964 AC: 499 AN: 5176

South Asian (SAS) AF: 0.437 AC: 2105 AN: 4812

European-Finnish (FIN) AF: 0.345 AC: 3632 AN: 10528

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

European-Non Finnish (NFE) AF: 0.366 AC: 24838 AN: 67954

Other (OTH) AF: 0.311 AC: 656 AN: 2112

Alfa AF: 0.331 Hom.: 11558

Bravo AF: 0.263

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		1.1
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: rs13354826; hg19: chr5-35225147;