6-22294758-A-T

Variant names:

• chr6-22294758-A-T
• rs2244502
• NM_000948.6:c.29-174T>A

Variant summary

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

The NM_000948.6(PRL):​c.29-174T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,108 control chromosomes in the GnomAD database, including 31,529 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 0.64 (31529 hom., cov: 32)
• Consequence: PRL NM_000948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRL	NM_000948.6	c.29-174T>A		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.29-174T>A		intron_variant	Intron 1 of 4	1	NM_000948.6	ENSP00000302150.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96778 AN: 151990 Hom.: 31512 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.637 AC: 96844 AN: 152108 Hom.: 31529 Cov.: 32 AF XY: 0.637 AC XY: 47340 AN XY: 74340

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.674

Alfa AF: 0.670 Hom.: 4324

Bravo AF: 0.631

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.62

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: rs2244502; hg19: chr6-22294987;