1-153843294-T-C

Variant names:

• chr1-153843294-T-C
• rs6427310
• NM_020699.4:c.-1-14946A>G

Variant summary

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

The NM_020699.4(GATAD2B):​c.-1-14946A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,628 control chromosomes in the GnomAD database, including 38,399 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 0.69 (38399 hom., cov: 28)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 3 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.-1-14946A>G		intron_variant	Intron 1 of 10	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.3-14946A>G		intron_variant	Intron 1 of 10		XP_047282071.1
GATAD2B	XM_047426117.1	c.-1-14946A>G		intron_variant	Intron 1 of 10		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.-1-14946A>G		intron_variant	Intron 1 of 10	1	NM_020699.4	ENSP00000357644.4

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104083 AN: 151510 Hom.: 38393 Cov.: 28

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.687 AC: 104126 AN: 151628 Hom.: 38399 Cov.: 28 AF XY: 0.683 AC XY: 50561 AN XY: 74074

African (AFR) AF: 0.428 AC: 17685 AN: 41318

American (AMR) AF: 0.733 AC: 11155 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3026 AN: 3468

East Asian (EAS) AF: 0.345 AC: 1768 AN: 5124

South Asian (SAS) AF: 0.672 AC: 3227 AN: 4804

European-Finnish (FIN) AF: 0.783 AC: 8216 AN: 10490

Middle Eastern (MID) AF: 0.762 AC: 221 AN: 290

European-Non Finnish (NFE) AF: 0.834 AC: 56622 AN: 67904

Other (OTH) AF: 0.733 AC: 1543 AN: 2104

Alfa AF: 0.738 Hom.: 6678

Bravo AF: 0.670

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.3
DANN	Benign	0.91
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: rs6427310; hg19: chr1-153815770;