8-117799781-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000127.3(EXT1):c.2172C>T(p.Leu724=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,014 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
EXT1
NM_000127.3 synonymous
NM_000127.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.289
Genes affected
EXT1 (HGNC:3512): (exostosin glycosyltransferase 1) This gene encodes an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type I form of multiple exostoses. [provided by RefSeq, Jul 2008]
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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=-0.43).
BP6
Variant 8-117799781-G-A is Benign according to our data. Variant chr8-117799781-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1132498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.289 with no splicing effect.
BS2
High AC in GnomAdExome4 at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EXT1 | NM_000127.3 | c.2172C>T | p.Leu724= | synonymous_variant | 11/11 | ENST00000378204.7 | NP_000118.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EXT1 | ENST00000378204.7 | c.2172C>T | p.Leu724= | synonymous_variant | 11/11 | 1 | NM_000127.3 | ENSP00000367446 | P1 | |
EXT1 | ENST00000684189.1 | n.1639C>T | non_coding_transcript_exon_variant | 11/11 | ||||||
EXT1 | ENST00000684443.1 | n.2298C>T | non_coding_transcript_exon_variant | 2/2 | ||||||
EXT1 | ENST00000437196.1 | downstream_gene_variant | 5 | ENSP00000407299 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251322Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135808
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727246
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74306
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Multiple congenital exostosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 05, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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