2-216420337-C-G
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014140.4(SMARCAL1):āc.901C>Gā(p.Pro301Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00139 in 1,614,122 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0074 ( 6 hom., cov: 32)
Exomes š: 0.00076 ( 14 hom. )
Consequence
SMARCAL1
NM_014140.4 missense
NM_014140.4 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 5.34
Genes affected
SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007854283).
BP6
Variant 2-216420337-C-G is Benign according to our data. Variant chr2-216420337-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-216420337-C-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0074 (1127/152252) while in subpopulation AFR AF= 0.0255 (1058/41542). AF 95% confidence interval is 0.0242. There are 6 homozygotes in gnomad4. There are 523 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCAL1 | NM_014140.4 | c.901C>G | p.Pro301Ala | missense_variant | 5/18 | ENST00000357276.9 | |
SMARCAL1 | NM_001127207.2 | c.901C>G | p.Pro301Ala | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCAL1 | ENST00000357276.9 | c.901C>G | p.Pro301Ala | missense_variant | 5/18 | 2 | NM_014140.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00739 AC: 1124AN: 152134Hom.: 6 Cov.: 32
GnomAD3 genomes
AF:
AC:
1124
AN:
152134
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: 0.00194 AC: 487AN: 251314Hom.: 4 AF XY: 0.00155 AC XY: 211AN XY: 135852
GnomAD3 exomes
AF:
AC:
487
AN:
251314
Hom.:
AF XY:
AC XY:
211
AN XY:
135852
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000764 AC: 1117AN: 1461870Hom.: 14 Cov.: 32 AF XY: 0.000716 AC XY: 521AN XY: 727236
GnomAD4 exome
AF:
AC:
1117
AN:
1461870
Hom.:
Cov.:
32
AF XY:
AC XY:
521
AN XY:
727236
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: 0.00740 AC: 1127AN: 152252Hom.: 6 Cov.: 32 AF XY: 0.00703 AC XY: 523AN XY: 74442
GnomAD4 genome
AF:
AC:
1127
AN:
152252
Hom.:
Cov.:
32
AF XY:
AC XY:
523
AN XY:
74442
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
107
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
289
Asia WGS
AF:
AC:
2
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Schimke immuno-osseous dysplasia Benign:6
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 02, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jul 27, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Jun 22, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;D;T;D
Polyphen
P;P;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at