Variant chr6-22287516-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000948.6(PRL):c.570G>A(p.Glu190Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,613,832 control chromosomes in the GnomAD database, including 3,615 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 0.046 ( 403 hom., cov: 33)

Exomes 𝑓: 0.037 ( 3212 hom. )

Consequence

PRL
NM_000948.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.763

Variant links:

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]

PRL links:

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]

CASC15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-0.763 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRL	NM_000948.6 link	c.570G>A	p.Glu190Glu	synonymous_variant	5/5	ENST00000306482.2	NP_000939.1	P01236Q5THQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000306482.2 link	c.570G>A	p.Glu190Glu	synonymous_variant	5/5	1	NM_000948.6	ENSP00000302150.1		P01236

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6940

AN:

152130

Hom.:

400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0538

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0788

AC:

19795

AN:

251350

Hom.:

1827

AF XY:

0.0725

AC XY:

9853

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.0951

Gnomad FIN exome

AF:

0.0526

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0577

GnomAD4 exome

AF:

0.0370

AC:

54120

AN:

1461584

Hom.:

3212

Cov.:

AF XY:

0.0378

AC XY:

27495

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.0306

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.0945

Gnomad4 FIN exome

AF:

0.0491

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0422

GnomAD4 genome

AF:

0.0458

AC:

6971

AN:

152248

Hom.:

403

Cov.:

AF XY:

0.0507

AC XY:

3777

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0313

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0538

Gnomad4 NFE

AF:

0.0189

Gnomad4 OTH

AF:

0.0444

Alfa

AF:

0.0326

Hom.:

178

Bravo

AF:

0.0527

Asia WGS

AF:

0.141

AC:

489

AN:

3478

EpiCase

AF:

0.0178

EpiControl

AF:

0.0212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.37

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over