Menu
GeneBe

6-22294535-C-T

Variant summary

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

The NM_000948.6(PRL):c.78G>A(p.Val26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,454 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 23 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 34 hom. )

Consequence

PRL
NM_000948.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.742
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]

Genome browser will be placed here

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=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-22294535-C-T is Benign according to our data. Variant chr6-22294535-C-T is described in ClinVar as [Benign]. Clinvar id is 782471.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=0.742 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 (1637/152280) while in subpopulation AFR AF= 0.037 (1536/41546). AF 95% confidence interval is 0.0354. There are 23 homozygotes in gnomad4. There are 751 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 23 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRLNM_000948.6 linkuse as main transcriptc.78G>A p.Val26= synonymous_variant 2/5 ENST00000306482.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRLENST00000306482.2 linkuse as main transcriptc.78G>A p.Val26= synonymous_variant 2/51 NM_000948.6 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0107
AC:
1626
AN:
152162
Hom.:
23
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0368
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00909
GnomAD3 exomes
AF:
0.00281
AC:
700
AN:
249058
Hom.:
11
AF XY:
0.00195
AC XY:
262
AN XY:
134642
show subpopulations
Gnomad AFR exome
AF:
0.0380
Gnomad AMR exome
AF:
0.00154
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000152
Gnomad OTH exome
AF:
0.00197
GnomAD4 exome
AF:
0.00116
AC:
1689
AN:
1461174
Hom.:
34
Cov.:
31
AF XY:
0.000971
AC XY:
706
AN XY:
726856
show subpopulations
Gnomad4 AFR exome
AF:
0.0387
Gnomad4 AMR exome
AF:
0.00195
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000810
Gnomad4 OTH exome
AF:
0.00313
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0107
AC:
1637
AN:
152280
Hom.:
23
Cov.:
32
AF XY:
0.0101
AC XY:
751
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0370
Gnomad4 AMR
AF:
0.00457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.00508
Hom.:
7
Bravo
AF:
0.0124
Asia WGS
AF:
0.00549
AC:
20
AN:
3478

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 testingInvitaeJan 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
2.5
Dann
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs6240; hg19: chr6-22294764; API