NM_014140.4:c.-137A>G

Variant names:

• chr2-216412607-A-G
• rs115172989
• NM_014140.4:c.-137A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014140.4(SMARCAL1):​c.-137A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 152,610 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (96 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (0 hom.)
• Consequence: SMARCAL1 NM_014140.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• Publications: 1 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-AS1 (HGNC:40555): (SMARCAL1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-216412607-A-G is Benign according to our data. Variant chr2-216412607-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 334285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0663 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.-137A>G		5_prime_UTR	Exon 1 of 18	NP_054859.2
	SMARCAL1	NM_001127207.2		c.-287A>G		upstream_gene	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.-137A>G		5_prime_UTR	Exon 1 of 18	ENSP00000349823.4	Q9NZC9
	SMARCAL1	ENST00000932386.1		c.-137A>G		5_prime_UTR	Exon 1 of 19	ENSP00000602445.1
	SMARCAL1	ENST00000860357.1		c.-137A>G		5_prime_UTR	Exon 1 of 18	ENSP00000530416.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3004 AN: 152200 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00340 AC: 1 AN: 294 Hom.: 0 Cov.: 0 AF XY: 0.00442 AC XY: 1 AN XY: 226

African (AFR) AF: 0.125 AC: 1 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 12

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 238

Other (OTH) AF: 0.00 AC: 0 AN: 16

GnomAD4 genome AF: 0.0198 AC: 3014 AN: 152316 Hom.: 96 Cov.: 32 AF XY: 0.0191 AC XY: 1421 AN XY: 74486

African (AFR) AF: 0.0684 AC: 2842 AN: 41570

American (AMR) AF: 0.00837 AC: 128 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68034

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.0250 Hom.: 49

Bravo AF: 0.0222

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Schimke immuno-osseous dysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.52
PhyloP100		-1.1
PromoterAI		0.042	Neutral
Mutation Taster		=298/2	polymorphism

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: rs115172989; hg19: chr2-217277330;