6-22287931-T-C

Position:

• chr6-22287931-T-C

Variant summary

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

The NM_000948.6(PRL):​c.493-338A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,014 control chromosomes in the GnomAD database, including 40,575 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 0.73 (40575 hom., cov: 31)
• Consequence: PRL NM_000948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRL	NM_000948.6	c.493-338A>G		intron_variant		ENST00000306482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRL	ENST00000306482.2	c.493-338A>G		intron_variant		1	NM_000948.6	P4

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110624 AN: 151896 Hom.: 40531 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.779

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.728 AC: 110720 AN: 152014 Hom.: 40575 Cov.: 31 AF XY: 0.730 AC XY: 54211 AN XY: 74296

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.753

Alfa AF: 0.747 Hom.: 38249

Bravo AF: 0.737

Asia WGS AF: 0.811 AC: 2821 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.032
DANN	Benign	0.26

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: rs1205960; hg19: chr6-22288160;