chr1-153849468-T-A

Variant names:

• chr1-153849468-T-A
• rs12129468
• NM_020699.4:c.-1-21120A>T

Variant summary

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

The NM_020699.4(GATAD2B):​c.-1-21120A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,132 control chromosomes in the GnomAD database, including 6,681 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 0.28 (6681 hom., cov: 32)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 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.-1-21120A>T		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.-1-21120A>T		intron	N/A	ENSP00000357644.4
	GATAD2B	ENST00000634544.1	TSL:5	c.-1-21120A>T		intron	N/A	ENSP00000489184.1
	GATAD2B	ENST00000634408.1	TSL:5	c.-1-21120A>T		intron	N/A	ENSP00000489595.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42679 AN: 152014 Hom.: 6678 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.281 AC: 42694 AN: 152132 Hom.: 6681 Cov.: 32 AF XY: 0.277 AC XY: 20583 AN XY: 74368

African (AFR) AF: 0.166 AC: 6880 AN: 41508

American (AMR) AF: 0.236 AC: 3604 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3468

East Asian (EAS) AF: 0.0574 AC: 298 AN: 5188

South Asian (SAS) AF: 0.299 AC: 1439 AN: 4818

European-Finnish (FIN) AF: 0.346 AC: 3665 AN: 10586

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24583 AN: 67968

Other (OTH) AF: 0.296 AC: 623 AN: 2108

Alfa AF: 0.325 Hom.: 1047

Bravo AF: 0.263

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.62
PhyloP100		0.29
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: rs12129468; hg19: chr1-153821944;