chr16-51151128-CGT-C

Variant names:

• chr16-51151128-CGT-C
• rs200502187
• NM_002968.3:c.76+36_76+37delAC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002968.3(SALL1):​c.76+36_76+37delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,475,558 control chromosomes in the GnomAD database, including 763 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (73 hom., cov: 32)
  • Exomes 𝑓: 0.030 (690 hom.)
• Consequence: SALL1 NM_002968.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.91
• Publications: 0 publications found

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]

SALL1 Gene-Disease associations (from GenCC):

• Townes-Brocks syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Townes-Brocks syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285367 (HGNC:58539):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-51151128-CGT-C is Benign according to our data. Variant chr16-51151128-CGT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258878.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 = 0.023 (3494/151976) while in subpopulation NFE AF = 0.0354 (2401/67894). AF 95% confidence interval is 0.0342. There are 73 homozygotes in GnomAd4. There are 1702 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3494 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002968.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.76+36_76+37delAC		intron	N/A	NP_002959.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.76+36_76+37delAC		intron	N/A	ENSP00000251020.4
	SALL1	ENST00000566102.1	TSL:1	c.76+36_76+37delAC		intron	N/A	ENSP00000455582.1
	SALL1	ENST00000440970.6	TSL:5	c.76+36_76+37delAC		intron	N/A	ENSP00000407914.2

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3496 AN: 151862 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00500

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00707

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0173

GnomAD2 exomes AF: 0.0282 AC: 4556 AN: 161520 AF XY: 0.0276

Gnomad AFR exome AF: 0.00868

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.00809

Gnomad EAS exome AF: 0.00314

Gnomad FIN exome AF: 0.0555

Gnomad NFE exome AF: 0.0432

Gnomad OTH exome AF: 0.0294

GnomAD4 exome AF: 0.0303 AC: 40126 AN: 1323582 Hom.: 690 AF XY: 0.0299 AC XY: 19678 AN XY: 659066

African (AFR) AF: 0.00507 AC: 154 AN: 30382

American (AMR) AF: 0.0124 AC: 460 AN: 37116

Ashkenazi Jewish (ASJ) AF: 0.00826 AC: 201 AN: 24334

East Asian (EAS) AF: 0.000936 AC: 34 AN: 36320

South Asian (SAS) AF: 0.00902 AC: 681 AN: 75462

European-Finnish (FIN) AF: 0.0501 AC: 2148 AN: 42864

Middle Eastern (MID) AF: 0.0103 AC: 40 AN: 3884

European-Non Finnish (NFE) AF: 0.0344 AC: 34995 AN: 1017838

Other (OTH) AF: 0.0255 AC: 1413 AN: 55382

GnomAD4 genome AF: 0.0230 AC: 3494 AN: 151976 Hom.: 73 Cov.: 32 AF XY: 0.0229 AC XY: 1702 AN XY: 74272

African (AFR) AF: 0.00499 AC: 207 AN: 41508

American (AMR) AF: 0.0166 AC: 254 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00686 AC: 33 AN: 4808

European-Finnish (FIN) AF: 0.0463 AC: 488 AN: 10548

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2401 AN: 67894

Other (OTH) AF: 0.0171 AC: 36 AN: 2106

Alfa AF: 0.0184 Hom.: 11

Bravo AF: 0.0201

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
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: rs200502187; hg19: chr16-51185039;