rs73072254

Variant names:

• chr2-216414437-G-A
• rs73072254
• NM_014140.4:c.-58-210G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Schimke immuno-osseous dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014140.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAL1	NM_014140.4	MANE Select	c.-58-210G>A		intron	N/A	NP_054859.2
	SMARCAL1	NM_001127207.2		c.-58-210G>A		intron	N/A	NP_001120679.1	Q9NZC9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAL1	ENST00000357276.9	TSL:2 MANE Select	c.-58-210G>A		intron	N/A	ENSP00000349823.4	Q9NZC9
	SMARCAL1	ENST00000358207.9	TSL:1	c.-58-210G>A		intron	N/A	ENSP00000350940.5	Q9NZC9
	SMARCAL1	ENST00000932386.1		c.-58-210G>A		intron	N/A	ENSP00000602445.1

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

African (AFR) AF: 0.0978 AC: 800 AN: 8184

American (AMR) AF: 0.00637 AC: 80 AN: 12562

Ashkenazi Jewish (ASJ) AF: 0.000128 AC: 1 AN: 7838

East Asian (EAS) AF: 0.0000687 AC: 1 AN: 14546

South Asian (SAS) AF: 0.000239 AC: 10 AN: 41768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12532

Middle Eastern (MID) AF: 0.00259 AC: 3 AN: 1160

European-Non Finnish (NFE) AF: 0.000219 AC: 36 AN: 164570

Other (OTH) AF: 0.00514 AC: 77 AN: 14994

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

African (AFR) AF: 0.0993 AC: 4123 AN: 41520

American (AMR) AF: 0.0113 AC: 173 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67998

Other (OTH) AF: 0.0213 AC: 45 AN: 2110

Alfa AF: 0.0315 Hom.: 134

Bravo AF: 0.0331

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.28
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73072254; hg19: chr2-217279160;