rs1139620

Variant names:

• chr1-153805372-C-T
• rs1139620
• NM_020699.4:c.*4805G>A

Variant summary

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

The NM_020699.4(GATAD2B):​c.*4805G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,972 control chromosomes in the GnomAD database, including 13,906 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 (13905 hom., cov: 30)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: GATAD2B NM_020699.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 18 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)

ENSG00000291199 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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 rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.*4805G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.*4805G>A		3_prime_UTR_variant	Exon 11 of 11		XP_047282071.1
GATAD2B	XM_047426117.1	c.*4805G>A		3_prime_UTR_variant	Exon 11 of 11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.*4805G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_020699.4	ENSP00000357644.4
GATAD2B	ENST00000637918.1	c.133+6359G>A		intron_variant	Intron 2 of 3	5		ENSP00000490724.1
ENSG00000291199	ENST00000820544.1	n.296+11167C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62304 AN: 151848 Hom.: 13901 Cov.: 30

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.410 AC: 62320 AN: 151966 Hom.: 13905 Cov.: 30 AF XY: 0.401 AC XY: 29777 AN XY: 74262

African (AFR) AF: 0.289 AC: 11953 AN: 41430

American (AMR) AF: 0.344 AC: 5253 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1985 AN: 3472

East Asian (EAS) AF: 0.0582 AC: 302 AN: 5186

South Asian (SAS) AF: 0.348 AC: 1677 AN: 4818

European-Finnish (FIN) AF: 0.431 AC: 4542 AN: 10546

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35111 AN: 67946

Other (OTH) AF: 0.436 AC: 918 AN: 2106

Alfa AF: 0.479 Hom.: 25893

Bravo AF: 0.394

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.8
DANN	Benign	0.54
PhyloP100		0.20
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: rs1139620; hg19: chr1-153777848;