3-141414608-G-A

Variant names:

• chr3-141414608-G-A
• rs1991431
• NM_001376113.1:c.-1+10577G>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.-1+10577G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,960 control chromosomes in the GnomAD database, including 19,528 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 0.49 (19528 hom., cov: 31)
• Consequence: ZBTB38 NM_001376113.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920
• Publications: 51 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB38	NM_001376113.1	c.-1+10577G>A		intron_variant	Intron 5 of 5	ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7	c.-1+10577G>A		intron_variant	Intron 5 of 5	6	NM_001376113.1	ENSP00000372635.5

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74066 AN: 151842 Hom.: 19490 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.488 AC: 74167 AN: 151960 Hom.: 19528 Cov.: 31 AF XY: 0.480 AC XY: 35670 AN XY: 74252

African (AFR) AF: 0.691 AC: 28625 AN: 41452

American (AMR) AF: 0.410 AC: 6266 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3464

East Asian (EAS) AF: 0.222 AC: 1145 AN: 5162

South Asian (SAS) AF: 0.287 AC: 1378 AN: 4806

European-Finnish (FIN) AF: 0.438 AC: 4628 AN: 10558

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29477 AN: 67916

Other (OTH) AF: 0.424 AC: 897 AN: 2114

Alfa AF: 0.453 Hom.: 32917

Bravo AF: 0.492

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.69
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1991431; hg19: chr3-141133450;