rs4434872

Variant names:

• chr1-153801800-T-C
• rs4434872
• ENST00000637918.1:c.133+9931A>G

Variant summary

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

The ENST00000427283.1(ENSG00000231827):​n.1961+3T>C variant causes a splice region, intron 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: ENSG00000231827 ENST00000427283.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 24 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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P, ClinGen

LOC124904425 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427283.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD2B	ENST00000637918.1	TSL:5	c.133+9931A>G		intron	N/A	ENSP00000490724.1	A0A1B0GW07
	ENSG00000231827	ENST00000427283.1	TSL:6	n.1961+3T>C		splice_region intron	N/A
	ENSG00000291199	ENST00000820544.1		n.296+7595T>C		intron	N/A

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

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 1.00 AC: 6 AN: 6

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 6 AN: 6

European-Finnish (FIN) AF: 0.783 AC: 346 AN: 442

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.840 AC: 257 AN: 306

Other (OTH) AF: 0.682 AC: 15 AN: 22

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

African (AFR) AF: 0.533 AC: 22113 AN: 41472

American (AMR) AF: 0.835 AC: 12773 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3059 AN: 3470

East Asian (EAS) AF: 0.437 AC: 2258 AN: 5168

South Asian (SAS) AF: 0.685 AC: 3310 AN: 4830

European-Finnish (FIN) AF: 0.778 AC: 8238 AN: 10584

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56474 AN: 68006

Other (OTH) AF: 0.769 AC: 1623 AN: 2110

Alfa AF: 0.789 Hom.: 158106

Bravo AF: 0.725

Asia WGS AF: 0.577 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.39
PhyloP100		-0.54

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4434872;

hg19: chr1-153774276;