rs12202764

chr6-22295104-T-A

Variant summary

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

The NM_000948.6(PRL):c.29-520A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,138 control chromosomes in the GnomAD database, including 4,332 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 0.23 (4332 hom., cov: 33)
• Consequence: PRL NM_000948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRL	NM_000948.6	c.29-520A>T		intron_variant		ENST00000306482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRL	ENST00000306482.2	c.29-520A>T		intron_variant		1	NM_000948.6	P4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35376 AN: 152020 Hom.: 4330 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.233 AC: 35399 AN: 152138 Hom.: 4332 Cov.: 33 AF XY: 0.228 AC XY: 16937 AN XY: 74382

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.00752

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.211

Alfa AF: 0.248 Hom.: 590

Bravo AF: 0.231

Asia WGS AF: 0.118 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.31
Dann	Benign	0.71

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: rs12202764; hg19: chr6-22295333;