5-35230278-G-C

Variant names:

• chr5-35230278-G-C
• rs10068521
• NM_000949.7:c.-116C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000949.7(PRLR):​c.-116C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 152,320 control chromosomes in the GnomAD database, including 274 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 0.052 (274 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRLR NM_000949.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0828 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	NM_000949.7	MANE Select	c.-116C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_000940.1
	PRLR	NM_000949.7	MANE Select	c.-116C>G		5_prime_UTR	Exon 1 of 10	NP_000940.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLR	ENST00000618457.5	TSL:1 MANE Select	c.-116C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000482954.1
	PRLR	ENST00000618457.5	TSL:1 MANE Select	c.-116C>G		5_prime_UTR	Exon 1 of 10	ENSP00000482954.1
	PRLR	ENST00000504500.5	TSL:3	c.-303C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000422867.1

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7946 AN: 152204 Hom.: 273 Cov.: 32

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.0361

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0507

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0522 AC: 7955 AN: 152320 Hom.: 274 Cov.: 32 AF XY: 0.0502 AC XY: 3741 AN XY: 74484

African (AFR) AF: 0.0852 AC: 3540 AN: 41566

American (AMR) AF: 0.0537 AC: 822 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 181 AN: 3472

East Asian (EAS) AF: 0.0362 AC: 187 AN: 5166

South Asian (SAS) AF: 0.0281 AC: 136 AN: 4832

European-Finnish (FIN) AF: 0.0199 AC: 212 AN: 10628

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0401 AC: 2725 AN: 68032

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0117 Hom.: 8

Bravo AF: 0.0589

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.89
PhyloP100		1.1
PromoterAI		-0.040	Neutral
Mutation Taster		=297/3	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: rs10068521; hg19: chr5-35230380;