1-153838088-C-T

Variant names:

• chr1-153838088-C-T
• rs7512766
• NM_020699.4:c.-1-9740G>A

Variant summary

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

The NM_020699.4(GATAD2B):​c.-1-9740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,048 control chromosomes in the GnomAD database, including 6,106 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 0.27 (6106 hom., cov: 32)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 4 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020699.4. 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
	GATAD2B	NM_020699.4	MANE Select	c.-1-9740G>A		intron	N/A	NP_065750.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD2B	ENST00000368655.5	TSL:1 MANE Select	c.-1-9740G>A		intron	N/A	ENSP00000357644.4
	GATAD2B	ENST00000634544.1	TSL:5	c.-1-9740G>A		intron	N/A	ENSP00000489184.1
	GATAD2B	ENST00000634408.1	TSL:5	c.-1-9740G>A		intron	N/A	ENSP00000489595.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41064 AN: 151930 Hom.: 6105 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.270 AC: 41092 AN: 152048 Hom.: 6106 Cov.: 32 AF XY: 0.275 AC XY: 20476 AN XY: 74326

African (AFR) AF: 0.138 AC: 5749 AN: 41510

American (AMR) AF: 0.384 AC: 5863 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1464 AN: 5172

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4824

European-Finnish (FIN) AF: 0.341 AC: 3595 AN: 10538

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20883 AN: 67976

Other (OTH) AF: 0.292 AC: 616 AN: 2110

Alfa AF: 0.240 Hom.: 1126

Bravo AF: 0.270

Asia WGS AF: 0.283 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-0.063
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: rs7512766; hg19: chr1-153810564;