rs9426935

Variant names:

• chr1-153796924-C-T
• rs9426935
• ENST00000637918.1:c.134-6848G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637918.1(GATAD2B):​c.134-6848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,982 control chromosomes in the GnomAD database, including 13,906 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13906 hom., cov: 32)
• Consequence: GATAD2B ENST00000637918.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834
• Publications: 18 publications found

Genes affected

GATAD2B (HGNC:30778): (GATA zinc finger domain containing 2B) This gene encodes a zinc finger protein transcriptional repressor. The encoded protein is part of the methyl-CpG-binding protein-1 complex, which represses gene expression by deacetylating methylated nucleosomes. Mutations in this gene are linked to intellectual disability and dysmorphic features associated with cognitive disability. [provided by RefSeq, Jun 2016]

GATAD2B Gene-Disease associations (from GenCC):

• severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Illumina, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000231827 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000637918.1	c.134-6848G>A		intron_variant	Intron 2 of 3	5		ENSP00000490724.1
ENSG00000231827	ENST00000427283.1	n.819+359C>T		intron_variant	Intron 3 of 10	6
ENSG00000291199	ENST00000820544.1	n.296+2719C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62326 AN: 151862 Hom.: 13902 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.410 AC: 62342 AN: 151982 Hom.: 13906 Cov.: 32 AF XY: 0.401 AC XY: 29790 AN XY: 74294

African (AFR) AF: 0.289 AC: 11962 AN: 41434

American (AMR) AF: 0.345 AC: 5272 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1985 AN: 3468

East Asian (EAS) AF: 0.0584 AC: 303 AN: 5186

South Asian (SAS) AF: 0.348 AC: 1674 AN: 4810

European-Finnish (FIN) AF: 0.430 AC: 4539 AN: 10548

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35109 AN: 67952

Other (OTH) AF: 0.436 AC: 920 AN: 2108

Alfa AF: 0.467 Hom.: 35034

Bravo AF: 0.394

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.54
PhyloP100		0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9426935; hg19: chr1-153769400;