chr5-35225515-A-G

Variant names:

• chr5-35225515-A-G
• rs10036454
• NM_000949.7:c.-106+4753T>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+4753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,152 control chromosomes in the GnomAD database, including 27,569 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 (27569 hom., cov: 33)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• 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: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	NM_000949.7	MANE Select	c.-106+4753T>C		intron	N/A	NP_000940.1	P16471-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	ENST00000618457.5	TSL:1 MANE Select	c.-106+4753T>C		intron	N/A	ENSP00000482954.1	P16471-1
	PRLR	ENST00000852369.1		c.-44+4753T>C		intron	N/A	ENSP00000522428.1
	PRLR	ENST00000852370.1		c.-399+4753T>C		intron	N/A	ENSP00000522429.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89172 AN: 152034 Hom.: 27550 Cov.: 33

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.586 AC: 89221 AN: 152152 Hom.: 27569 Cov.: 33 AF XY: 0.585 AC XY: 43502 AN XY: 74394

African (AFR) AF: 0.411 AC: 17042 AN: 41508

American (AMR) AF: 0.589 AC: 9011 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1704 AN: 5180

South Asian (SAS) AF: 0.684 AC: 3294 AN: 4818

European-Finnish (FIN) AF: 0.618 AC: 6536 AN: 10580

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47286 AN: 67992

Other (OTH) AF: 0.593 AC: 1253 AN: 2112

Alfa AF: 0.645 Hom.: 17235

Bravo AF: 0.570

Asia WGS AF: 0.499 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.50
PhyloP100		-0.29
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: rs10036454; hg19: chr5-35225617;