12-45040603-C-T

Variant names:

• chr12-45040603-C-T
• rs1495042
• NM_001004329.3:c.404-4489G>A

Variant summary

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

The NM_001004329.3(DBX2):​c.404-4489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,848 control chromosomes in the GnomAD database, including 12,616 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 0.38 (12616 hom., cov: 31)
• Consequence: DBX2 NM_001004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 2 publications found

Genes affected

DBX2 (HGNC:33186): (developing brain homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307871 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBX2	NM_001004329.3	MANE Select	c.404-4489G>A		intron	N/A	NP_001004329.2	Q6ZNG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBX2	ENST00000332700.6	TSL:2 MANE Select	c.404-4489G>A		intron	N/A	ENSP00000331470.6	Q6ZNG2
	ENSG00000307871	ENST00000829537.1		n.241-2869C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57552 AN: 151732 Hom.: 12618 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.379 AC: 57558 AN: 151848 Hom.: 12616 Cov.: 31 AF XY: 0.384 AC XY: 28510 AN XY: 74218

African (AFR) AF: 0.158 AC: 6531 AN: 41438

American (AMR) AF: 0.353 AC: 5382 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1593 AN: 3466

East Asian (EAS) AF: 0.382 AC: 1960 AN: 5136

South Asian (SAS) AF: 0.674 AC: 3248 AN: 4816

European-Finnish (FIN) AF: 0.474 AC: 4983 AN: 10506

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32241 AN: 67928

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.431 Hom.: 18553

Bravo AF: 0.354

Asia WGS AF: 0.473 AC: 1643 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.9
DANN	Benign	0.73
PhyloP100		0.37
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: rs1495042; hg19: chr12-45434386;