2-216414437-G-A

Position:

• chr2-216414437-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014140.4(SMARCAL1):​c.-58-210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 430,360 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (205 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (37 hom.)
• Consequence: SMARCAL1 NM_014140.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-216414437-G-A is Benign according to our data. Variant chr2-216414437-G-A is described in ClinVar as [Benign]. Clinvar id is 1259167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAL1	NM_014140.4	c.-58-210G>A		intron_variant		ENST00000357276.9
SMARCAL1	NM_001127207.2	c.-58-210G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAL1	ENST00000357276.9	c.-58-210G>A		intron_variant		2	NM_014140.4	P1

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4365 AN: 152088 Hom.: 205 Cov.: 33

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0216

GnomAD4 exome AF: 0.00362 AC: 1008 AN: 278154 Hom.: 37 Cov.: 0 AF XY: 0.00279 AC XY: 420 AN XY: 150420

Gnomad4 AFR exome AF: 0.0978

Gnomad4 AMR exome AF: 0.00637

Gnomad4 ASJ exome AF: 0.000128

Gnomad4 EAS exome AF: 0.0000687

Gnomad4 SAS exome AF: 0.000239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00514

GnomAD4 genome AF: 0.0287 AC: 4367 AN: 152206 Hom.: 205 Cov.: 33 AF XY: 0.0281 AC XY: 2094 AN XY: 74428

Gnomad4 AFR AF: 0.0993

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0155 Hom.: 18

Bravo AF: 0.0331

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs73072254; hg19: chr2-217279160;