chr10-110584175-T-G
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005445.4(SMC3):c.1092-8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,310 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_005445.4 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- Cornelia de Lange syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- Cornelia de Lange syndrome 3Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00899 AC: 1368AN: 152232Hom.: 20 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00264 AC: 662AN: 251142 AF XY: 0.00206 show subpopulations
GnomAD4 exome AF: 0.00105 AC: 1528AN: 1460960Hom.: 16 Cov.: 32 AF XY: 0.000944 AC XY: 686AN XY: 726836 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00900 AC: 1371AN: 152350Hom.: 20 Cov.: 32 AF XY: 0.00846 AC XY: 630AN XY: 74508 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Cornelia de Lange syndrome 3 Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at