dbSNP rs4434872: LOC124904425:n.158T>C (chr1-153801800-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_007066633.1(LOC124904425):n.158T>C variant causes a non coding transcript exon 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

LOC124904425
XR_007066633.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.535

Publications

24 publications found

Variant links:

Genes affected

LOC124904425 (HGNC:):

LOC124904425 links:

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)

GATAD2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124904425	XR_007066633.1 link	n.158T>C		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
GATAD2B	ENST00000637918.1 link	c.133+9931A>G	intron_variant	Intron 2 of 3	5	ENSP00000490724.1	A0A1B0GW07
ENSG00000231827	ENST00000427283.1 link	n.1961+3T>C	splice_region_variant, intron_variant	Intron 10 of 10	6
ENSG00000291199	ENST00000820544.1 link	n.296+7595T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110649

AN:

152022

Hom.:

41882

Cov.:

show subpopulations

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.:

AF XY:

0.794

AC XY:

427

AN XY:

538

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.783

AC:

346

AN:

442

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.840

AC:

257

AN:

306

Other (OTH)

AF:

0.682

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.728

AC:

110734

AN:

152140

Hom.:

41912

Cov.:

AF XY:

0.725

AC XY:

53888

AN XY:

74376

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1431

2862

4292

5723

7154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

(source)

DANN

Benign

0.39

PhyloP100

-0.54

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over