rs6440003

Variant names:

• chr3-141375367-G-A
• rs6440003
• NM_001376113.1:c.-235+5421G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376113.1(ZBTB38):​c.-235+5421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,082 control chromosomes in the GnomAD database, including 24,046 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 0.53 (24046 hom., cov: 32)
• Consequence: ZBTB38 NM_001376113.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 78 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB38	NM_001376113.1	c.-235+5421G>A		intron_variant	Intron 2 of 5	ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7	c.-235+5421G>A		intron_variant	Intron 2 of 5	6	NM_001376113.1	ENSP00000372635.5

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80801 AN: 151964 Hom.: 23994 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.532 AC: 80919 AN: 152082 Hom.: 24046 Cov.: 32 AF XY: 0.525 AC XY: 39052 AN XY: 74348

African (AFR) AF: 0.816 AC: 33887 AN: 41508

American (AMR) AF: 0.440 AC: 6722 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3470

East Asian (EAS) AF: 0.325 AC: 1678 AN: 5168

South Asian (SAS) AF: 0.324 AC: 1560 AN: 4816

European-Finnish (FIN) AF: 0.441 AC: 4663 AN: 10570

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29698 AN: 67958

Other (OTH) AF: 0.449 AC: 947 AN: 2108

Alfa AF: 0.457 Hom.: 69359

Bravo AF: 0.541

Asia WGS AF: 0.316 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs6440003; hg19: chr3-141094209;