6-22287516-C-T

Variant names:

• chr6-22287516-C-T
• rs6239
• NM_000948.6:c.570G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000948.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRL	NM_000948.6	MANE Select	c.570G>A	p.Glu190Glu	synonymous	Exon 5 of 5	NP_000939.1	Q5THQ0
	PRL	NM_001163558.3		c.570G>A	p.Glu190Glu	synonymous	Exon 6 of 6	NP_001157030.1	Q5THQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRL	ENST00000306482.2	TSL:1 MANE Select	c.570G>A	p.Glu190Glu	synonymous	Exon 5 of 5	ENSP00000302150.1	P01236
	PRL	ENST00000617911.4	TSL:1	c.573G>A	p.Glu191Glu	synonymous	Exon 5 of 5	ENSP00000480195.1	Q5I0G2
	PRL	ENST00000651757.1		c.390G>A	p.Glu130Glu	synonymous	Exon 5 of 5	ENSP00000499154.1	A0A494C1P2

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

GnomAD2 exomes AF: 0.0788 AC: 19795 AN: 251350 AF XY: 0.0725

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 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

African (AFR) AF: 0.0306 AC: 1023 AN: 33474

American (AMR) AF: 0.221 AC: 9857 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 564 AN: 26128

East Asian (EAS) AF: 0.226 AC: 8967 AN: 39674

South Asian (SAS) AF: 0.0945 AC: 8145 AN: 86176

European-Finnish (FIN) AF: 0.0491 AC: 2623 AN: 53410

Middle Eastern (MID) AF: 0.0375 AC: 216 AN: 5764

European-Non Finnish (NFE) AF: 0.0181 AC: 20180 AN: 1111898

Other (OTH) AF: 0.0422 AC: 2545 AN: 60378

GnomAD4 genome AF: 0.0458 AC: 6971 AN: 152248 Hom.: 403 Cov.: 33 AF XY: 0.0507 AC XY: 3777 AN XY: 74440

African (AFR) AF: 0.0313 AC: 1301 AN: 41554

American (AMR) AF: 0.120 AC: 1833 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1228 AN: 5160

South Asian (SAS) AF: 0.103 AC: 497 AN: 4820

European-Finnish (FIN) AF: 0.0538 AC: 570 AN: 10600

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0189 AC: 1283 AN: 68024

Other (OTH) AF: 0.0444 AC: 94 AN: 2116

Alfa AF: 0.0337 Hom.: 495

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.37
DANN	Benign	0.89
PhyloP100		-0.76
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: rs6239; hg19: chr6-22287745; COSMIC: COSV60591337;