rs724016

Positions:

• chr3-141386728-A-G

Variant summary

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

The NM_001376113.1(ZBTB38):​c.-171-144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,470 control chromosomes in the GnomAD database, including 21,902 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 0.51 (21862 hom., cov: 32)
  • Exomes 𝑓: 0.44 (40 hom.)
• Consequence: ZBTB38 NM_001376113.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001376113.1	c.-171-144A>G		intron_variant		ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7	c.-171-144A>G		intron_variant			NM_001376113.1	ENSP00000372635	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77973 AN: 151914 Hom.: 21824 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.438 AC: 191 AN: 436 Hom.: 40 Cov.: 0 AF XY: 0.427 AC XY: 112 AN XY: 262

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.514 AC: 78074 AN: 152034 Hom.: 21862 Cov.: 32 AF XY: 0.507 AC XY: 37660 AN XY: 74352

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.437

Alfa AF: 0.431 Hom.: 28413

Bravo AF: 0.521

Asia WGS AF: 0.307 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs724016; hg19: chr3-141105570; COSMIC: COSV72286607;