dbSNP rs6789653: ZBTB38:c.1-10241G>A (chr3-141432148-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001350099.2(ZBTB38):c.-190-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 985,264 control chromosomes in the GnomAD database, including 53,391 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5633 hom., cov: 32)

Exomes 𝑓: 0.33 ( 47758 hom. )

Consequence

ZBTB38
NM_001350099.2 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.926

Publications

20 publications found

Variant links:

Genes affected

ZBTB38 (HGNC:26636): (zinc finger and BTB domain containing 38) The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types. [provided by RefSeq, Jun 2010]

ZBTB38 links:

ENSG00000309977 (HGNC:):

ENSG00000309977 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350099.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZBTB38	NM_001376113.1	MANE Select	c.1-10241G>A	intron	N/A	NP_001363042.1	Q8NAP3
ZBTB38	NM_001080412.3		c.1-10241G>A	intron	N/A	NP_001073881.2	Q8NAP3
ZBTB38	NM_001350099.2		c.-190-4G>A	splice_region intron	N/A	NP_001337028.1	Q8NAP3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZBTB38	ENST00000321464.7	TSL:6 MANE Select	c.1-10241G>A	intron	N/A	ENSP00000372635.5	Q8NAP3
ZBTB38	ENST00000509883.5	TSL:1	c.1-10241G>A	intron	N/A	ENSP00000424254.1	D6RBC4
ZBTB38	ENST00000509842.5	TSL:1	c.1-10241G>A	intron	N/A	ENSP00000426931.1	D6RE69

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37465

AN:

152074

Hom.:

5635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.335

AC:

278843

AN:

833072

Hom.:

47758

Cov.:

AF XY:

0.335

AC XY:

128904

AN XY:

384702

show subpopulations

African (AFR)

AF:

0.108

AC:

1703

AN:

15784

American (AMR)

AF:

0.145

AC:

143

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1683

AN:

5152

East Asian (EAS)

AF:

0.00441

AC:

AN:

3632

South Asian (SAS)

AF:

0.178

AC:

2933

AN:

16460

European-Finnish (FIN)

AF:

0.330

AC:

AN:

276

Middle Eastern (MID)

AF:

0.256

AC:

415

AN:

1620

European-Non Finnish (NFE)

AF:

0.347

AC:

264082

AN:

761862

Other (OTH)

AF:

0.285

AC:

7777

AN:

27302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

9875

19751

29626

39502

49377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11436

22872

34308

45744

57180

<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:

0.246

AC:

37465

AN:

152192

Hom.:

5633

Cov.:

AF XY:

0.240

AC XY:

17879

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.123

AC:

5127

AN:

41546

American (AMR)

AF:

0.168

AC:

2564

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1142

AN:

3472

East Asian (EAS)

AF:

0.00347

AC:

AN:

5188

South Asian (SAS)

AF:

0.162

AC:

780

AN:

4828

European-Finnish (FIN)

AF:

0.364

AC:

3845

AN:

10554

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.341

AC:

23165

AN:

68006

Other (OTH)

AF:

0.222

AC:

468

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1406

2812

4219

5625

7031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.277

Hom.:

4763

Bravo

AF:

0.226

Asia WGS

AF:

0.0770

AC:

270

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

(source)

DANN

Benign

0.80

PhyloP100

-0.93

PromoterAI

-0.13

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over