rs2066514
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The NM_014140.4(SMARCAL1):c.1851+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000418 in 1,613,934 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014140.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCAL1 | NM_014140.4 | c.1851+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000357276.9 | |||
SMARCAL1 | NM_001127207.2 | c.1851+5G>A | splice_donor_5th_base_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCAL1 | ENST00000357276.9 | c.1851+5G>A | splice_donor_5th_base_variant, intron_variant | 2 | NM_014140.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00115 AC: 175AN: 152026Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000689 AC: 173AN: 251226Hom.: 0 AF XY: 0.000560 AC XY: 76AN XY: 135800
GnomAD4 exome AF: 0.000342 AC: 500AN: 1461790Hom.: 2 Cov.: 32 AF XY: 0.000304 AC XY: 221AN XY: 727208
GnomAD4 genome ? AF: 0.00115 AC: 175AN: 152144Hom.: 0 Cov.: 30 AF XY: 0.00108 AC XY: 80AN XY: 74380
ClinVar
Submissions by phenotype
Schimke immuno-osseous dysplasia Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | SMARCAL1 NM_014140.3 exon 11 c.1851+5G>A: This variant has not been reported in the literature but is present in 0.3% (84/24022) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-217311886-G-A). This variant is present in ClinVar (Variation ID:463146). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant; splice prediction tools are unclear whether this variant may or may not affect splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 09, 2017 | - - |
SMARCAL1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2021 | 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at