2-216450941-C-T

Position:

chr2-216450941-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014140.4(SMARCAL1):c.1947C>T(p.Asp649=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,614,180 control chromosomes in the GnomAD database, including 470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 34 hom., cov: 32)

Exomes 𝑓: 0.021 ( 436 hom. )

Consequence

SMARCAL1
NM_014140.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -2.87

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 2-216450941-C-T is Benign according to our data. Variant chr2-216450941-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.87 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.018 (2739/152312) while in subpopulation SAS AF= 0.0263 (127/4826). AF 95% confidence interval is 0.0232. There are 34 homozygotes in gnomad4. There are 1395 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAL1	NM_014140.4 linkuse as main transcript	c.1947C>T	p.Asp649=	synonymous_variant	12/18	ENST00000357276.9	NP_054859.2
SMARCAL1	NM_001127207.2 linkuse as main transcript	c.1947C>T	p.Asp649=	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.1947C>T	p.Asp649=	synonymous_variant	12/18	2	NM_014140.4	ENSP00000349823	P1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2740

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0640

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0242

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0231

AC:

5801

AN:

251308

Hom.:

102

AF XY:

0.0248

AC XY:

3364

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00308

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0738

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0304

Gnomad FIN exome

AF:

0.0278

Gnomad NFE exome

AF:

0.0250

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0210

AC:

30729

AN:

1461868

Hom.:

436

Cov.:

AF XY:

0.0218

AC XY:

15860

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00248

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0712

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0311

Gnomad4 FIN exome

AF:

0.0280

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0239

GnomAD4 genome

AF:

0.0180

AC:

2739

AN:

152312

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1395

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.0157

Gnomad4 ASJ

AF:

0.0640

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.0288

Gnomad4 NFE

AF:

0.0242

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0231

Hom.:

Bravo

AF:

0.0150

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0249

EpiControl

AF:

0.0235

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Schimke immuno-osseous dysplasia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:2Other:1

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Focal segmental glomerulosclerosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 27, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.6

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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