9-95506383-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000264.5(PTCH1):c.394+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,607,116 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 8 hom. )
Consequence
PTCH1
NM_000264.5 intron
NM_000264.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0450
Genes affected
PTCH1 (HGNC:9585): (patched 1) This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. Hedgehog signaling is important in embryonic development and tumorigenesis. The encoded protein is the receptor for the secreted hedgehog ligands, which include sonic hedgehog, indian hedgehog and desert hedgehog. Following binding by one of the hedgehog ligands, the encoded protein is trafficked away from the primary cilium, relieving inhibition of the G-protein-coupled receptor smoothened, which results in activation of downstream signaling. Mutations of this gene have been associated with basal cell nevus syndrome and holoprosencephaly. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 9-95506383-G-A is Benign according to our data. Variant chr9-95506383-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000092 (14/152192) while in subpopulation SAS AF= 0.00291 (14/4818). AF 95% confidence interval is 0.00176. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.394+24C>T | intron_variant | ENST00000331920.11 | |||
PTCH1 | NM_001083603.3 | c.391+24C>T | intron_variant | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.394+24C>T | intron_variant | 5 | NM_000264.5 | A2 | |||
PTCH1 | ENST00000437951.6 | c.391+24C>T | intron_variant | 5 | NM_001083603.3 | ||||
ENST00000604104.1 | n.149G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 152080Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000538 AC: 129AN: 240000Hom.: 1 AF XY: 0.000712 AC XY: 93AN XY: 130538
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GnomAD4 exome AF: 0.000243 AC: 353AN: 1454924Hom.: 8 Cov.: 31 AF XY: 0.000351 AC XY: 254AN XY: 723574
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74416
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at