16-51137582-CAGAG-CAG

Position:

• chr16-51137582-CAGAG-CAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002968.3(SALL1):​c.3535-32_3535-31del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 1,368,248 control chromosomes in the GnomAD database, including 1,093 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (104 hom., cov: 31)
  • Exomes 𝑓: 0.056 (989 hom.)
• Consequence: SALL1 NM_002968.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.239

Genes affected

SALL1 (HGNC:10524): (spalt like transcription factor 1) The protein encoded by this gene is a zinc finger transcriptional repressor and may be part of the NuRD histone deacetylase complex (HDAC). Defects in this gene are a cause of Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 16-51137582-CAG-C is Benign according to our data. Variant chr16-51137582-CAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 258869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3	c.3535-32_3535-31del		intron_variant		ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9	c.3535-32_3535-31del		intron_variant		1	NM_002968.3	ENSP00000251020	P2

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4788 AN: 150082 Hom.: 104 Cov.: 31

Gnomad AFR AF: 0.00682

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0273

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0347

GnomAD4 exome AF: 0.0555 AC: 67607 AN: 1218058 Hom.: 989 AF XY: 0.0564 AC XY: 34198 AN XY: 605994

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.0541

Gnomad4 ASJ exome AF: 0.0495

Gnomad4 EAS exome AF: 0.00724

Gnomad4 SAS exome AF: 0.0636

Gnomad4 FIN exome AF: 0.0709

Gnomad4 NFE exome AF: 0.0573

Gnomad4 OTH exome AF: 0.0518

GnomAD4 genome AF: 0.0319 AC: 4787 AN: 150190 Hom.: 104 Cov.: 31 AF XY: 0.0324 AC XY: 2378 AN XY: 73306

Gnomad4 AFR AF: 0.00680

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0273

Gnomad4 EAS AF: 0.00176

Gnomad4 SAS AF: 0.0362

Gnomad4 FIN AF: 0.0652

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0344

Bravo AF: 0.0281

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs142249003; hg19: chr16-51171493;