Variant 1-46511045-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_172225.2(DMBX1):c.444C>T(p.Ala148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,818 control chromosomes in the GnomAD database, including 31,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.25 ( 6010 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25974 hom. )

Consequence

DMBX1
NM_172225.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.08

Variant links:

Genes affected

DMBX1 (HGNC:19026): (diencephalon/mesencephalon homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DMBX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-46511045-C-T is Benign according to our data. Variant chr1-46511045-C-T is described in ClinVar as [Benign]. Clinvar id is 3061007.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-4.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DMBX1	NM_172225.2 linkuse as main transcript	c.444C>T	p.Ala148=	synonymous_variant	5/6	ENST00000360032.4
DMBX1	NM_001387776.1 linkuse as main transcript	c.459C>T	p.Ala153=	synonymous_variant	4/5
DMBX1	NM_147192.4 linkuse as main transcript	c.459C>T	p.Ala153=	synonymous_variant	5/6
DMBX1	NM_001387775.1 linkuse as main transcript	c.444C>T	p.Ala148=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMBX1	ENST00000360032.4 linkuse as main transcript	c.444C>T	p.Ala148=	synonymous_variant	5/6	1	NM_172225.2	P1	Q8NFW5-2

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38542

AN:

151966

Hom.:

5999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.210

AC:

52779

AN:

250736

Hom.:

6474

AF XY:

0.210

AC XY:

28452

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.445

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.296

Gnomad SAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.178

AC:

260083

AN:

1461734

Hom.:

25974

Cov.:

AF XY:

0.180

AC XY:

131196

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.456

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.254

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.242

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.254

AC:

38596

AN:

152084

Hom.:

6010

Cov.:

AF XY:

0.258

AC XY:

19204

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.440

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.285

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.198

Hom.:

1692

Bravo

AF:

0.254

Asia WGS

AF:

0.255

AC:

891

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMBX1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0060

DANN

Benign

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over