rs2066527

Positions:

chr2-216451064-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014140.4(SMARCAL1):c.2070T>C(p.Thr690=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,612,622 control chromosomes in the GnomAD database, including 12,913 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 Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 878 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12035 hom. )

Consequence

SMARCAL1
NM_014140.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0003744

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.289

Variant links:

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]

SMARCAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-216451064-T-C is Benign according to our data. Variant chr2-216451064-T-C is described in ClinVar as [Benign]. Clinvar id is 260341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-216451064-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.289 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAL1	NM_014140.4 linkuse as main transcript	c.2070T>C	p.Thr690=	splice_region_variant, synonymous_variant	12/18	ENST00000357276.9	NP_054859.2
SMARCAL1	NM_001127207.2 linkuse as main transcript	c.2070T>C	p.Thr690=	splice_region_variant, synonymous_variant	12/18		NP_001120679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCAL1	ENST00000357276.9 linkuse as main transcript	c.2070T>C	p.Thr690=	splice_region_variant, synonymous_variant	12/18	2	NM_014140.4	ENSP00000349823	P1

Frequencies

GnomAD3 genomes

AF:

0.0965

AC:

14671

AN:

152098

Hom.:

875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0549

Gnomad ASJ

AF:

0.0830

Gnomad EAS

AF:

0.00828

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.0838

GnomAD3 exomes

AF:

0.109

AC:

27225

AN:

249660

Hom.:

1889

AF XY:

0.117

AC XY:

15870

AN XY:

135180

show subpopulations

Gnomad AFR exome

AF:

0.0458

Gnomad AMR exome

AF:

0.0440

Gnomad ASJ exome

AF:

0.0797

Gnomad EAS exome

AF:

0.00648

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.0971

GnomAD4 exome

AF:

0.122

AC:

178521

AN:

1460406

Hom.:

12035

Cov.:

AF XY:

0.125

AC XY:

90644

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.0487

Gnomad4 AMR exome

AF:

0.0463

Gnomad4 ASJ exome

AF:

0.0773

Gnomad4 EAS exome

AF:

0.00458

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0965

AC:

14683

AN:

152216

Hom.:

878

Cov.:

AF XY:

0.0974

AC XY:

7250

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0486

Gnomad4 AMR

AF:

0.0548

Gnomad4 ASJ

AF:

0.0830

Gnomad4 EAS

AF:

0.00830

Gnomad4 SAS

AF:

0.186

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.0825

Alfa

AF:

0.111

Hom.:

2325

Bravo

AF:

0.0836

Asia WGS

AF:

0.102

AC:

353

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.115

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Schimke immuno-osseous dysplasia

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 21, 2019	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.8

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over