rs6240
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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
NM_000948.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.742
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
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
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
?
Synonymous conserved (PhyloP=0.742 with no splicing effect.
BS1
?
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
?
High Homozygotes in GnomAd4 at 23 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRL | NM_000948.6 | c.78G>A | p.Val26= | synonymous_variant | 2/5 | ENST00000306482.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRL | ENST00000306482.2 | c.78G>A | p.Val26= | synonymous_variant | 2/5 | 1 | NM_000948.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0107 AC: 1626AN: 152162Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.00281 AC: 700AN: 249058Hom.: 11 AF XY: 0.00195 AC XY: 262AN XY: 134642
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GnomAD4 exome AF: 0.00116 AC: 1689AN: 1461174Hom.: 34 Cov.: 31 AF XY: 0.000971 AC XY: 706AN XY: 726856
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GnomAD4 genome ? AF: 0.0107 AC: 1637AN: 152280Hom.: 23 Cov.: 32 AF XY: 0.0101 AC XY: 751AN XY: 74458
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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 submitter | clinical testing | Invitae | Jan 25, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at