rs12202764

Variant names:

• chr6-22295104-T-A
• rs12202764
• NM_000948.6:c.29-520A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRL	NM_000948.6	c.29-520A>T		intron_variant	Intron 1 of 4	ENST00000306482.2	NP_000939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000306482.2	c.29-520A>T		intron_variant	Intron 1 of 4	1	NM_000948.6	ENSP00000302150.1

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

African (AFR) AF: 0.274 AC: 11384 AN: 41498

American (AMR) AF: 0.172 AC: 2628 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3466

East Asian (EAS) AF: 0.00752 AC: 39 AN: 5188

South Asian (SAS) AF: 0.185 AC: 890 AN: 4820

European-Finnish (FIN) AF: 0.226 AC: 2391 AN: 10574

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16566 AN: 67976

Other (OTH) AF: 0.211 AC: 445 AN: 2110

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
PhyloP100		-0.62
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: rs12202764; hg19: chr6-22295333;