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6-22292568-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000948.6(PRL):c.282C>T(p.Pro94=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.73
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.73 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 28 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRLNM_000948.6 linkuse as main transcriptc.282C>T p.Pro94= synonymous_variant 3/5 ENST00000306482.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRLENST00000306482.2 linkuse as main transcriptc.282C>T p.Pro94= synonymous_variant 3/51 NM_000948.6 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0107
AC:
1625
AN:
152086
Hom.:
28
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00298
AC:
749
AN:
251424
Hom.:
9
AF XY:
0.00233
AC XY:
316
AN XY:
135894
show subpopulations
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 SAS exome
AF:
0.000294
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0367
Gnomad4 AMR exome
AF:
0.00344
Gnomad4 ASJ exome
AF:
0.000344
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000122
Gnomad4 OTH exome
AF:
0.00252
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0107
AC:
1630
AN:
152202
Hom.:
28
Cov.:
32
AF XY:
0.0106
AC XY:
788
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0361
Gnomad4 AMR
AF:
0.00628
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00514
Hom.:
7
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
1.1
Dann
Benign
0.83

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.

Other links and lift over

dbSNP: rs114131603; hg19: chr6-22292797; API