5-35145261-T-C

Position:

• chr5-35145261-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000949.7(PRLR):​c.-105-27139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,092 control chromosomes in the GnomAD database, including 56,683 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 0.85 (56683 hom., cov: 31)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-105-27139A>G		intron_variant		ENST00000618457.5	NP_000940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRLR	ENST00000618457.5	c.-105-27139A>G		intron_variant		1	NM_000949.7	ENSP00000482954.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129340 AN: 151974 Hom.: 56653 Cov.: 31

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.851 AC: 129418 AN: 152092 Hom.: 56683 Cov.: 31 AF XY: 0.853 AC XY: 63430 AN XY: 74364

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.921

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.862

Alfa AF: 0.935 Hom.: 127423

Bravo AF: 0.837

Asia WGS AF: 0.895 AC: 3112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.54
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs9292571; hg19: chr5-35145363;