2-216482705-C-T

Variant names:

• chr2-216482705-C-T
• rs71579835
• NM_014140.4:c.2626-33C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014140.4(SMARCAL1):​c.2626-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 1,613,902 control chromosomes in the GnomAD database, including 1,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (105 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1603 hom.)
• Consequence: SMARCAL1 NM_014140.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.446
• Publications: 2 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]

RPL37A-DT (HGNC:40510): (RPL37A divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-216482705-C-T is Benign according to our data. Variant chr2-216482705-C-T is described in ClinVar as Benign. ClinVar VariationId is 1283732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0317 (4832/152282) while in subpopulation NFE AF = 0.0482 (3281/68020). AF 95% confidence interval is 0.0469. There are 105 homozygotes in GnomAd4. There are 2354 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 105 AR gene

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.2626-33C>T		intron	N/A	NP_054859.2
	SMARCAL1	NM_001127207.2		c.2626-33C>T		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.2626-33C>T		intron	N/A	ENSP00000349823.4	Q9NZC9
	SMARCAL1	ENST00000358207.9	TSL:1	c.2626-33C>T		intron	N/A	ENSP00000350940.5	Q9NZC9
	SMARCAL1	ENST00000392128.6	TSL:1	c.2152-33C>T		intron	N/A	ENSP00000375974.2	H7BYI2

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4834 AN: 152164 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.00883

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0373 AC: 9318 AN: 249730 AF XY: 0.0392

Gnomad AFR exome AF: 0.00681

Gnomad AMR exome AF: 0.0134

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0547

Gnomad NFE exome AF: 0.0505

Gnomad OTH exome AF: 0.0331

GnomAD4 exome AF: 0.0443 AC: 64722 AN: 1461620 Hom.: 1603 Cov.: 32 AF XY: 0.0445 AC XY: 32324 AN XY: 727138

African (AFR) AF: 0.00627 AC: 210 AN: 33480

American (AMR) AF: 0.0145 AC: 649 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 746 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39696

South Asian (SAS) AF: 0.0450 AC: 3878 AN: 86216

European-Finnish (FIN) AF: 0.0552 AC: 2950 AN: 53406

Middle Eastern (MID) AF: 0.0326 AC: 188 AN: 5768

European-Non Finnish (NFE) AF: 0.0485 AC: 53936 AN: 1111810

Other (OTH) AF: 0.0358 AC: 2161 AN: 60390

GnomAD4 genome AF: 0.0317 AC: 4832 AN: 152282 Hom.: 105 Cov.: 33 AF XY: 0.0316 AC XY: 2354 AN XY: 74460

African (AFR) AF: 0.00880 AC: 366 AN: 41574

American (AMR) AF: 0.0173 AC: 265 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4820

European-Finnish (FIN) AF: 0.0543 AC: 576 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0482 AC: 3281 AN: 68020

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0381 Hom.: 24

Bravo AF: 0.0277

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

ClinVar submissions

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	-0.82
CADD	Benign	8.9
DANN	Benign	0.73
PhyloP100		0.45
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: rs71579835; hg19: chr2-217347428;