rs1127091

Positions:

• chr1-153806936-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020699.4(GATAD2B):​c.*3241T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,944 control chromosomes in the GnomAD database, including 14,562 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 0.42 (14556 hom., cov: 30)
  • Exomes 𝑓: 0.47 (6 hom.)
• Consequence: GATAD2B NM_020699.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATAD2B	NM_020699.4	c.*3241T>C		3_prime_UTR_variant	11/11	ENST00000368655.5
GATAD2B	XM_047426115.1	c.*3241T>C		3_prime_UTR_variant	11/11
GATAD2B	XM_047426117.1	c.*3241T>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATAD2B	ENST00000368655.5	c.*3241T>C		3_prime_UTR_variant	11/11	1	NM_020699.4	P1
GATAD2B	ENST00000637918.1	c.135+4795T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64303 AN: 151790 Hom.: 14547 Cov.: 30

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.472 AC: 17 AN: 36 Hom.: 6 Cov.: 0 AF XY: 0.462 AC XY: 12 AN XY: 26

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.423 AC: 64327 AN: 151908 Hom.: 14556 Cov.: 30 AF XY: 0.417 AC XY: 30925 AN XY: 74226

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.448

Alfa AF: 0.493 Hom.: 34129

Bravo AF: 0.415

Asia WGS AF: 0.280 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs1127091; hg19: chr1-153779412;