rs114131603

Variant names:

• chr6-22292568-G-A
• rs114131603
• NM_000948.6:c.282C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-22292568-G-A
• chr6-22292568-G-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000948.6(PRL):​c.282C>T​(p.Pro94Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,010 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (28 hom.)
• Consequence: PRL NM_000948.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-22292568-G-A is Benign according to our data. Variant chr6-22292568-G-A is described in ClinVar as [Benign]. Clinvar id is 768067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1630/152202) while in subpopulation AFR AF = 0.0361 (1498/41514). AF 95% confidence interval is 0.0346. There are 28 homozygotes in GnomAd4. There are 788 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRL	NM_000948.6	c.282C>T	p.Pro94Pro	synonymous_variant	Exon 3 of 5	ENST00000306482.2	NP_000939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000306482.2	c.282C>T	p.Pro94Pro	synonymous_variant	Exon 3 of 5	1	NM_000948.6	ENSP00000302150.1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1625 AN: 152086 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00298 AC: 749 AN: 251424 AF XY: 0.00233

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00117 AC: 1714 AN: 1461808 Hom.: 28 Cov.: 31 AF XY: 0.00103 AC XY: 746 AN XY: 727206

African (AFR) AF: 0.0367 AC: 1230 AN: 33478

American (AMR) AF: 0.00344 AC: 154 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.000122 AC: 136 AN: 1111966

Other (OTH) AF: 0.00252 AC: 152 AN: 60388

GnomAD4 genome AF: 0.0107 AC: 1630 AN: 152202 Hom.: 28 Cov.: 32 AF XY: 0.0106 AC XY: 788 AN XY: 74394

African (AFR) AF: 0.0361 AC: 1498 AN: 41514

American (AMR) AF: 0.00628 AC: 96 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68016

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00483 Hom.: 8

Bravo AF: 0.0122

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-1.7
Mutation Taster		=99/1	polymorphism

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: rs114131603; hg19: chr6-22292797;