5-35171919-G-C

Variant names:

• chr5-35171919-G-C
• rs4703505
• NM_000949.7:c.-105-53797C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000949.7(PRLR):​c.-105-53797C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.-105-53797C>G		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.-105-53797C>G		intron	N/A	ENSP00000482954.1	P16471-1
	PRLR	ENST00000509839.5	TSL:1	c.-106+23184C>G		intron	N/A	ENSP00000427060.1	D6RD41
	PRLR	ENST00000852369.1		c.-44+58349C>G		intron	N/A	ENSP00000522428.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151920 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151920 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74186

African (AFR) AF: 0.00 AC: 0 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.32
PhyloP100		0.38

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: rs4703505; hg19: chr5-35172021;