chr7-129189198-G-GGCT
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_005631.5(SMO):c.67_69dup(p.Leu23dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,146,950 control chromosomes in the GnomAD database, including 303 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.020 ( 55 hom., cov: 32)
Exomes 𝑓: 0.023 ( 248 hom. )
Consequence
SMO
NM_005631.5 inframe_insertion
NM_005631.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.23
Genes affected
SMO (HGNC:11119): (smoothened, frizzled class receptor) The protein encoded by this gene is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [provided by RefSeq, Jul 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 7-129189198-G-GGCT is Benign according to our data. Variant chr7-129189198-G-GGCT is described in ClinVar as [Likely_benign]. Clinvar id is 769335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0201 (3038/151452) while in subpopulation NFE AF= 0.0296 (2004/67736). AF 95% confidence interval is 0.0285. There are 55 homozygotes in gnomad4. There are 1535 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 55 SM gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMO | NM_005631.5 | c.67_69dup | p.Leu23dup | inframe_insertion | 1/12 | ENST00000249373.8 | |
SMO | XM_047420759.1 | c.-438_-436dup | 5_prime_UTR_variant | 1/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMO | ENST00000249373.8 | c.67_69dup | p.Leu23dup | inframe_insertion | 1/12 | 1 | NM_005631.5 | P1 | |
SMO | ENST00000655644.1 | c.67_69dup | p.Leu23dup | inframe_insertion, NMD_transcript_variant | 1/12 |
Frequencies
GnomAD3 genomes ? AF: 0.0201 AC: 3038AN: 151350Hom.: 55 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3038
AN:
151350
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0165 AC: 6AN: 364Hom.: 0 AF XY: 0.0143 AC XY: 3AN XY: 210
GnomAD3 exomes
AF:
AC:
6
AN:
364
Hom.:
AF XY:
AC XY:
3
AN XY:
210
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0229 AC: 22797AN: 995498Hom.: 248 Cov.: 15 AF XY: 0.0231 AC XY: 10940AN XY: 473586
GnomAD4 exome
AF:
AC:
22797
AN:
995498
Hom.:
Cov.:
15
AF XY:
AC XY:
10940
AN XY:
473586
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0201 AC: 3038AN: 151452Hom.: 55 Cov.: 32 AF XY: 0.0207 AC XY: 1535AN XY: 74006
GnomAD4 genome
?
AF:
AC:
3038
AN:
151452
Hom.:
Cov.:
32
AF XY:
AC XY:
1535
AN XY:
74006
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 08, 2019 | This variant is associated with the following publications: (PMID: 30709382, 23349881, 23826113) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 09, 2019 | - - |
SMO-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 09, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at