rs6789653

Positions:

• chr3-141432148-G-A
• chr3-141432148-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376113.1(ZBTB38):​c.1-10241G>A variant causes a 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. 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_001376113.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001376113.1	c.1-10241G>A		intron_variant		ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7	c.1-10241G>A		intron_variant			NM_001376113.1	ENSP00000372635	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37465 AN: 152074 Hom.: 5635 Cov.: 32

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.: 31 AF XY: 0.335 AC XY: 128904 AN XY: 384702

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.00441

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.246 AC: 37465 AN: 152192 Hom.: 5633 Cov.: 32 AF XY: 0.240 AC XY: 17879 AN XY: 74390

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.222

Alfa AF: 0.272 Hom.: 2276

Bravo AF: 0.226

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs6789653; hg19: chr3-141150990; COSMIC: COSV58541383;