rs7414227

Variant names:

• chr1-153876520-G-A
• rs7414227
• NM_020699.4:c.-2+46213C>T

Variant summary

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

The NM_020699.4(GATAD2B):​c.-2+46213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,930 control chromosomes in the GnomAD database, including 13,959 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 0.41 (13959 hom., cov: 31)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 17 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.-2+46213C>T		intron_variant	Intron 1 of 10	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.2+39932C>T		intron_variant	Intron 1 of 10		XP_047282071.1
GATAD2B	XM_047426117.1	c.-2+22336C>T		intron_variant	Intron 1 of 10		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.-2+46213C>T		intron_variant	Intron 1 of 10	1	NM_020699.4	ENSP00000357644.4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62412 AN: 151810 Hom.: 13956 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.411 AC: 62425 AN: 151930 Hom.: 13959 Cov.: 31 AF XY: 0.402 AC XY: 29829 AN XY: 74258

African (AFR) AF: 0.288 AC: 11943 AN: 41446

American (AMR) AF: 0.347 AC: 5284 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1983 AN: 3468

East Asian (EAS) AF: 0.0591 AC: 306 AN: 5178

South Asian (SAS) AF: 0.340 AC: 1640 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4540 AN: 10522

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35227 AN: 67936

Other (OTH) AF: 0.436 AC: 920 AN: 2110

Alfa AF: 0.417 Hom.: 9244

Bravo AF: 0.395

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		0.15
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: rs7414227; hg19: chr1-153848996;