Variant 2-216482705-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.446

Variant links:

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 links:

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

RPL37A-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 105 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAL1	NM_014140.4 linkuse as main transcript	c.2626-33C>T		intron_variant		ENST00000357276.9	NP_054859.2
SMARCAL1	NM_001127207.2 linkuse as main transcript	c.2626-33C>T		intron_variant			NP_001120679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCAL1	ENST00000357276.9 linkuse as main transcript	c.2626-33C>T		intron_variant		2	NM_014140.4	ENSP00000349823	P1
RPL37A-DT	ENST00000453157.1 linkuse as main transcript	n.283-3446G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4834

AN:

152164

Hom.:

105

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0373

AC:

9318

AN:

249730

Hom.:

217

AF XY:

0.0392

AC XY:

5307

AN XY:

135498

show subpopulations

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 SAS exome

AF:

0.0440

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.:

AF XY:

0.0445

AC XY:

32324

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00627

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0450

Gnomad4 FIN exome

AF:

0.0552

Gnomad4 NFE exome

AF:

0.0485

Gnomad4 OTH exome

AF:

0.0358

GnomAD4 genome

AF:

0.0317

AC:

4832

AN:

152282

Hom.:

105

Cov.:

AF XY:

0.0316

AC XY:

2354

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00880

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0254

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0340

Gnomad4 FIN

AF:

0.0543

Gnomad4 NFE

AF:

0.0482

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0381

Hom.:

Bravo

AF:

0.0277

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Aug 31, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.9

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over