rs4434872

Positions:

• chr1-153801800-T-C

Variant summary

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

The ENST00000427283.1(ENSG00000231827):​n.1961+3T>C variant causes a splice donor region, intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,934 control chromosomes in the GnomAD database, including 42,175 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 0.73 (41912 hom., cov: 34)
  • Exomes 𝑓: 0.80 (263 hom.)
• Consequence: ENST00000427283.1 splice_donor_region, intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

Genes affected

LOC124904425 (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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904425	XR_007066633.1	n.158T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000427283.1	n.1961+3T>C		splice_donor_region_variant, intron_variant, non_coding_transcript_variant
GATAD2B	ENST00000637918.1	c.135+9931A>G		intron_variant		5		ENSP00000490724

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110649 AN: 152022 Hom.: 41882 Cov.: 34

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.805 AC: 639 AN: 794 Hom.: 263 Cov.: 0 AF XY: 0.794 AC XY: 427 AN XY: 538

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.783

Gnomad4 NFE exome AF: 0.840

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.728 AC: 110734 AN: 152140 Hom.: 41912 Cov.: 34 AF XY: 0.725 AC XY: 53888 AN XY: 74376

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.769

Alfa AF: 0.798 Hom.: 62963

Bravo AF: 0.725

Asia WGS AF: 0.577 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4434872; hg19: chr1-153774276;