rs12133923

Positions:

• chr1-153800764-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000427283.1(ENSG00000231827):​n.1511+52C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,362 control chromosomes in the GnomAD database, including 14,563 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 (14498 hom., cov: 31)
  • Exomes 𝑓: 0.44 (65 hom.)
• Consequence: ENST00000427283.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

Genes affected

(HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000427283.1	n.1511+52C>A		intron_variant, non_coding_transcript_variant
GATAD2B	ENST00000637918.1	c.136-10688G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64129 AN: 151624 Hom.: 14489 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.444 AC: 275 AN: 620 Hom.: 65 AF XY: 0.424 AC XY: 174 AN XY: 410

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.423 AC: 64153 AN: 151742 Hom.: 14498 Cov.: 31 AF XY: 0.416 AC XY: 30849 AN XY: 74166

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.449

Alfa AF: 0.474 Hom.: 2645

Bravo AF: 0.414

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12133923; hg19: chr1-153773240;