chr1-153818025-C-T

Variant names:

• chr1-153818025-C-T
• rs4363451
• NM_020699.4:c.729+15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020699.4(GATAD2B):​c.729+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,579,648 control chromosomes in the GnomAD database, including 75,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6099 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69450 hom.)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.803
• Publications: 13 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)

ENSG00000291199 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-153818025-C-T is Benign according to our data. Variant chr1-153818025-C-T is described in ClinVar as Benign. ClinVar VariationId is 1285293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.729+15G>A		intron_variant	Intron 5 of 10	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.732+15G>A		intron_variant	Intron 5 of 10		XP_047282071.1
GATAD2B	XM_047426117.1	c.729+15G>A		intron_variant	Intron 5 of 10		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.729+15G>A		intron_variant	Intron 5 of 10	1	NM_020699.4	ENSP00000357644.4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40777 AN: 152012 Hom.: 6100 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.295

GnomAD2 exomes AF: 0.322 AC: 73044 AN: 226758 AF XY: 0.325

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.309 AC: 440395 AN: 1427518 Hom.: 69450 Cov.: 31 AF XY: 0.310 AC XY: 219783 AN XY: 708702

African (AFR) AF: 0.117 AC: 3734 AN: 31790

American (AMR) AF: 0.431 AC: 16325 AN: 37840

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 7534 AN: 24452

East Asian (EAS) AF: 0.302 AC: 11728 AN: 38810

South Asian (SAS) AF: 0.334 AC: 27258 AN: 81610

European-Finnish (FIN) AF: 0.344 AC: 18202 AN: 52870

Middle Eastern (MID) AF: 0.353 AC: 1966 AN: 5570

European-Non Finnish (NFE) AF: 0.307 AC: 335964 AN: 1095702

Other (OTH) AF: 0.300 AC: 17684 AN: 58874

GnomAD4 genome AF: 0.268 AC: 40790 AN: 152130 Hom.: 6099 Cov.: 32 AF XY: 0.273 AC XY: 20311 AN XY: 74344

African (AFR) AF: 0.126 AC: 5233 AN: 41524

American (AMR) AF: 0.386 AC: 5897 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1478 AN: 5174

South Asian (SAS) AF: 0.333 AC: 1609 AN: 4826

European-Finnish (FIN) AF: 0.343 AC: 3615 AN: 10554

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20995 AN: 67982

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

Alfa AF: 0.293 Hom.: 2981

Bravo AF: 0.268

Asia WGS AF: 0.285 AC: 994 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.80
PromoterAI		0.010	Neutral
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: rs4363451; hg19: chr1-153790501; COSMIC: COSV64083611; COSMIC: COSV64083611;