chr6-22292324-G-A

Variant names:

• chr6-22292324-G-A
• rs7739889
• NM_000948.6:c.312+214C>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.312+214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,080 control chromosomes in the GnomAD database, including 3,389 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 0.20 (3389 hom., cov: 33)
• Consequence: PRL NM_000948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRL	NM_000948.6	c.312+214C>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.312+214C>T		intron_variant	Intron 3 of 4	1	NM_000948.6	ENSP00000302150.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31160 AN: 151962 Hom.: 3387 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.00692

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.205 AC: 31175 AN: 152080 Hom.: 3389 Cov.: 33 AF XY: 0.200 AC XY: 14847 AN XY: 74344

African (AFR) AF: 0.200 AC: 8289 AN: 41480

American (AMR) AF: 0.147 AC: 2246 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3468

East Asian (EAS) AF: 0.00693 AC: 36 AN: 5194

South Asian (SAS) AF: 0.156 AC: 753 AN: 4828

European-Finnish (FIN) AF: 0.235 AC: 2487 AN: 10570

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15939 AN: 67950

Other (OTH) AF: 0.189 AC: 400 AN: 2114

Alfa AF: 0.224 Hom.: 2019

Bravo AF: 0.198

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.80
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7739889; hg19: chr6-22292553; COSMIC: COSV60593892;