NM_000948.6:c.313-956C>T

Variant names:

• chr6-22291309-G-A
• rs849885
• NM_000948.6:c.313-956C>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.313-956C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,010 control chromosomes in the GnomAD database, including 18,372 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 0.47 (18372 hom., cov: 32)
• Consequence: PRL NM_000948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRL	NM_000948.6	c.313-956C>T		intron_variant	Intron 3 of 4	ENST00000306482.2	NP_000939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000306482.2	c.313-956C>T		intron_variant	Intron 3 of 4	1	NM_000948.6	ENSP00000302150.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71804 AN: 151892 Hom.: 18353 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.473 AC: 71866 AN: 152010 Hom.: 18372 Cov.: 32 AF XY: 0.480 AC XY: 35694 AN XY: 74292

African (AFR) AF: 0.298 AC: 12343 AN: 41462

American (AMR) AF: 0.619 AC: 9459 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1851 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4571 AN: 5178

South Asian (SAS) AF: 0.536 AC: 2583 AN: 4816

European-Finnish (FIN) AF: 0.452 AC: 4760 AN: 10534

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34447 AN: 67960

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.492 Hom.: 13768

Bravo AF: 0.481

Asia WGS AF: 0.690 AC: 2399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.31
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: rs849885; hg19: chr6-22291538;