1-153806760-C-G

Variant names:

• chr1-153806760-C-G
• rs1127092
• NM_020699.4:c.*3417G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020699.4(GATAD2B):​c.*3417G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000046 (0 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: GATAD2B NM_020699.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 7 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.*3417G>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.*3417G>C		3_prime_UTR_variant	Exon 11 of 11		XP_047282071.1
GATAD2B	XM_047426117.1	c.*3417G>C		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.*3417G>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_020699.4	ENSP00000357644.4
GATAD2B	ENST00000637918.1	c.133+4971G>C		intron_variant	Intron 2 of 3	5		ENSP00000490724.1
ENSG00000291199	ENST00000820544.1	n.296+12555C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 6 AN: 130286 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000844

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000361

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000163

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000461 AC: 6 AN: 130286 Hom.: 0 Cov.: 26 AF XY: 0.0000802 AC XY: 5 AN XY: 62380

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000297 AC: 1 AN: 33668

American (AMR) AF: 0.0000844 AC: 1 AN: 11852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3118

East Asian (EAS) AF: 0.00 AC: 0 AN: 4928

South Asian (SAS) AF: 0.00 AC: 0 AN: 4108

European-Finnish (FIN) AF: 0.000361 AC: 3 AN: 8310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000163 AC: 1 AN: 61434

Other (OTH) AF: 0.00 AC: 0 AN: 1750

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.56
PhyloP100		-0.069

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: rs1127092; hg19: chr1-153779236;