chr9-95468705-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000264.5(PTCH1):c.2250+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,601,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
PTCH1
NM_000264.5 intron
NM_000264.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.317
Publications
0 publications found
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]
PTCH1 Gene-Disease associations (from GenCC):
- basal cell nevus syndrome 1Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
- holoprosencephaly 7Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- nevoid basal cell carcinoma syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
- holoprosencephalyInheritance: AD Classification: LIMITED Submitted by: Illumina
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 9-95468705-G-A is Benign according to our data. Variant chr9-95468705-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255676.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2250+46C>T | intron_variant | Intron 14 of 23 | 5 | NM_000264.5 | ENSP00000332353.6 | |||
PTCH1 | ENST00000437951.6 | c.2247+46C>T | intron_variant | Intron 14 of 23 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152092Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
6
AN:
152092
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000280 AC: 7AN: 249908 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
AF:
AC:
7
AN:
249908
AF XY:
Gnomad AFR exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000124 AC: 18AN: 1449714Hom.: 0 Cov.: 32 AF XY: 0.00000970 AC XY: 7AN XY: 721988 show subpopulations
GnomAD4 exome
AF:
AC:
18
AN:
1449714
Hom.:
Cov.:
32
AF XY:
AC XY:
7
AN XY:
721988
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33206
American (AMR)
AF:
AC:
14
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26064
East Asian (EAS)
AF:
AC:
0
AN:
39644
South Asian (SAS)
AF:
AC:
3
AN:
85576
European-Finnish (FIN)
AF:
AC:
0
AN:
53310
Middle Eastern (MID)
AF:
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1101462
Other (OTH)
AF:
AC:
0
AN:
60008
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74416 show subpopulations
GnomAD4 genome
AF:
AC:
5
AN:
152210
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74416
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41520
American (AMR)
AF:
AC:
5
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5182
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68014
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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10
<30
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>80
Age
Alfa
AF:
Hom.:
Bravo
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Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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