Variant chr2-216412526-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014140.4(SMARCAL1):c.-218C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,270 control chromosomes in the GnomAD database, including 4,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4913 hom., cov: 33)

Exomes 𝑓: 0.24 ( 3 hom. )

Consequence

SMARCAL1
NM_014140.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.512

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:

SMARCAL1-AS1 (HGNC:40555): (SMARCAL1 antisense RNA 1)

SMARCAL1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-216412526-C-T is Benign according to our data. Variant chr2-216412526-C-T is described in ClinVar as [Benign]. Clinvar id is 334280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-216412526-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAL1	NM_014140.4 linkuse as main transcript	c.-218C>T		5_prime_UTR_variant	1/18	ENST00000357276.9
SMARCAL1-AS1	XR_001739881.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAL1	ENST00000357276.9 linkuse as main transcript	c.-218C>T		5_prime_UTR_variant	1/18	2	NM_014140.4	P1
SMARCAL1-AS1	ENST00000457694.1 linkuse as main transcript	n.171G>A		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34784

AN:

152098

Hom.:

4914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0558

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.241

AC:

AN:

Hom.:

Cov.:

AF XY:

0.237

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.275

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.228

AC:

34769

AN:

152216

Hom.:

4913

Cov.:

AF XY:

0.230

AC XY:

17126

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0556

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.262

Hom.:

911

Bravo

AF:

0.214

Asia WGS

AF:

0.233

AC:

809

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Schimke immuno-osseous dysplasia

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.2

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

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