6-22287516-C-T

Position:

• chr6-22287516-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

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:):

ACMG classification

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	c.570G>A	p.Glu190Glu	synonymous_variant	5/5	ENST00000306482.2	NP_000939.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6940 AN: 152130 Hom.: 400 Cov.: 33

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

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.: 31 AF XY: 0.0378 AC XY: 27495 AN XY: 727084

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.: 33 AF XY: 0.0507 AC XY: 3777 AN XY: 74440

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

Other links and lift over

dbSNP: rs6239; hg19: chr6-22287745; COSMIC: COSV60591337;