12-45040603-C-T

Position:

• chr12-45040603-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105369742 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBX2	NM_001004329.3	c.404-4489G>A		intron_variant		ENST00000332700.6	NP_001004329.2
LOC105369742	XR_944885.3	n.204-2869C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBX2	ENST00000332700.6	c.404-4489G>A		intron_variant		2	NM_001004329.3	ENSP00000331470.6

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.404

Alfa AF: 0.443 Hom.: 14750

Bravo AF: 0.354

Asia WGS AF: 0.473 AC: 1643 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.9
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs1495042; hg19: chr12-45434386;