rs2744117

Variant names:

• chr6-22302610-G-T
• rs2744117
• NM_001163558.3:c.-98+150C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163558.3(PRL):​c.-98+150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 152,140 control chromosomes in the GnomAD database, including 649 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 0.076 (649 hom., cov: 32)
• Consequence: PRL NM_001163558.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRL	NM_001163558.3	c.-98+150C>A		intron_variant	Intron 1 of 5		NP_001157030.1
PRL	XM_011514753.3	c.-98+150C>A		intron_variant	Intron 1 of 5		XP_011513055.1
PRL	XM_011514754.3	c.-111+150C>A		intron_variant	Intron 1 of 6		XP_011513056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000651757.1	c.-98+150C>A		intron_variant	Intron 1 of 4			ENSP00000499154.1
PRL	ENST00000651245.1	c.-98+150C>A		intron_variant	Intron 1 of 4			ENSP00000498773.1
CASC15	ENST00000561912.3	n.569+11622G>T		intron_variant	Intron 4 of 10	5
CASC15	ENST00000651569.1	n.505+11622G>T		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11596 AN: 152022 Hom.: 647 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0828

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

GnomAD4 genome AF: 0.0762 AC: 11598 AN: 152140 Hom.: 649 Cov.: 32 AF XY: 0.0782 AC XY: 5816 AN XY: 74372

African (AFR) AF: 0.0283 AC: 1176 AN: 41512

American (AMR) AF: 0.145 AC: 2222 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1193 AN: 5170

South Asian (SAS) AF: 0.118 AC: 570 AN: 4818

European-Finnish (FIN) AF: 0.0412 AC: 437 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5456 AN: 67968

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0825 Hom.: 235

Bravo AF: 0.0809

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.28
PhyloP100		-0.32
PromoterAI		-0.0064	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2744117; hg19: chr6-22302839;