rs3756824

Positions:

• chr6-22298508-C-G
• chr6-22298508-C-T

Variant summary

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

The NM_001163558.3(PRL):​c.-97-1429G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,214 control chromosomes in the GnomAD database, including 405 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 0.044 (405 hom., cov: 33)
• Consequence: PRL NM_001163558.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434

Genes affected

PRL (HGNC:9445): (prolactin) This gene encodes the anterior pituitary hormone prolactin. This secreted hormone is a growth regulator for many tissues, including cells of the immune system. It may also play a role in cell survival by suppressing apoptosis, and it is essential for lactation. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRL	NM_001163558.3	c.-97-1429G>C		intron_variant
PRL	XM_011514753.3	c.-97-1429G>C		intron_variant
PRL	XM_011514754.3	c.-97-1429G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRL	ENST00000651245.1	c.-97-1429G>C		intron_variant
PRL	ENST00000651757.1	c.-97-1429G>C		intron_variant
CASC15	ENST00000561912.3	n.569+7520C>G		intron_variant, non_coding_transcript_variant		5
CASC15	ENST00000651569.1	n.505+7520C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6637 AN: 152096 Hom.: 407 Cov.: 33

Gnomad AFR AF: 0.00973

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0436 AC: 6638 AN: 152214 Hom.: 405 Cov.: 33 AF XY: 0.0496 AC XY: 3689 AN XY: 74404

Gnomad4 AFR AF: 0.00972

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0112 Hom.: 1

Bravo AF: 0.0452

Asia WGS AF: 0.168 AC: 585 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3756824; hg19: chr6-22298737;