21-46191631-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002340.6(LSS):c.2067+250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 152,244 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.026 ( 66 hom., cov: 33)
Consequence
LSS
NM_002340.6 intron
NM_002340.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.260
Genes affected
LSS (HGNC:6708): (lanosterol synthase) The protein encoded by this gene catalyzes the conversion of (S)-2,3 oxidosqualene to lanosterol. The encoded protein is a member of the terpene cyclase/mutase family and catalyzes the first step in the biosynthesis of cholesterol, steroid hormones, and vitamin D. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 21-46191631-G-A is Benign according to our data. Variant chr21-46191631-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211649.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0261 (3967/152244) while in subpopulation AFR AF= 0.0372 (1546/41530). AF 95% confidence interval is 0.0357. There are 66 homozygotes in gnomad4. There are 1860 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 66 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LSS | NM_002340.6 | c.2067+250C>T | intron_variant | ENST00000397728.8 | |||
LSS | NM_001001438.3 | c.2067+250C>T | intron_variant | ||||
LSS | NM_001145436.2 | c.2034+250C>T | intron_variant | ||||
LSS | NM_001145437.2 | c.1827+250C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LSS | ENST00000397728.8 | c.2067+250C>T | intron_variant | 1 | NM_002340.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0261 AC: 3967AN: 152126Hom.: 66 Cov.: 33
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0261 AC: 3967AN: 152244Hom.: 66 Cov.: 33 AF XY: 0.0250 AC XY: 1860AN XY: 74436
GnomAD4 genome
?
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152244
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1860
AN XY:
74436
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3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2019 | - - |
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