2-216414393-G-A

Position:

• chr2-216414393-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014140.4(SMARCAL1):​c.-58-254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 352,382 control chromosomes in the GnomAD database, including 400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (168 hom., cov: 33)
  • Exomes 𝑓: 0.028 (232 hom.)
• Consequence: SMARCAL1 NM_014140.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.796

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-216414393-G-A is Benign according to our data. Variant chr2-216414393-G-A is described in ClinVar as [Benign]. Clinvar id is 1287616.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAL1	NM_014140.4	c.-58-254G>A		intron_variant		ENST00000357276.9	NP_054859.2
SMARCAL1	NM_001127207.2	c.-58-254G>A		intron_variant			NP_001120679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCAL1	ENST00000357276.9	c.-58-254G>A		intron_variant		2	NM_014140.4	ENSP00000349823.4

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5008 AN: 152138 Hom.: 170 Cov.: 33

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.00830

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00954

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0276 AC: 5531 AN: 200126 Hom.: 232 Cov.: 0 AF XY: 0.0317 AC XY: 3473 AN XY: 109506

Gnomad4 AFR exome AF: 0.0626

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0209

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.0623

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00921

Gnomad4 OTH exome AF: 0.0236

GnomAD4 genome AF: 0.0329 AC: 5002 AN: 152256 Hom.: 168 Cov.: 33 AF XY: 0.0343 AC XY: 2552 AN XY: 74462

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.00830

Gnomad4 NFE AF: 0.00956

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0219 Hom.: 8

Bravo AF: 0.0343

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.39

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: rs58617956; hg19: chr2-217279116;