chr5-35221344-C-G

Variant names:

• chr5-35221344-C-G
• rs7731880
• NM_000949.7:c.-106+8924G>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+8924G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,180 control chromosomes in the GnomAD database, including 1,000 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 0.11 (1000 hom., cov: 32)
• Consequence: PRLR NM_000949.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• 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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRLR	NM_000949.7	c.-106+8924G>C		intron_variant	Intron 1 of 9	ENST00000618457.5	NP_000940.1
PRLR	XM_024446131.2	c.59+8924G>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+8924G>C		intron_variant	Intron 1 of 9	1	NM_000949.7	ENSP00000482954.1
PRLR	ENST00000504500.5	c.-293+8924G>C		intron_variant	Intron 1 of 4	3		ENSP00000422867.1
PRLR	ENST00000515839.1	c.-269+8924G>C		intron_variant	Intron 1 of 4	2		ENSP00000421864.1
PRLR	ENST00000508107.5	n.-106+8924G>C		intron_variant	Intron 1 of 6	3		ENSP00000427236.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16683 AN: 152062 Hom.: 999 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.110 AC: 16705 AN: 152180 Hom.: 1000 Cov.: 32 AF XY: 0.109 AC XY: 8140 AN XY: 74386

African (AFR) AF: 0.131 AC: 5424 AN: 41502

American (AMR) AF: 0.0827 AC: 1265 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 484 AN: 3470

East Asian (EAS) AF: 0.157 AC: 813 AN: 5178

South Asian (SAS) AF: 0.0587 AC: 283 AN: 4824

European-Finnish (FIN) AF: 0.121 AC: 1283 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6805 AN: 68002

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.110 Hom.: 130

Bravo AF: 0.110

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.9
DANN	Benign	0.70
PhyloP100		0.053
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: rs7731880; hg19: chr5-35221446;