Variant 1-46511199-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_172225.2(DMBX1):c.598G>C(p.Ala200Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00772 in 1,613,426 control chromosomes in the GnomAD database, including 869 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 429 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 440 hom. )

Consequence

DMBX1
NM_172225.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

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 (MetaRNN=0.0015186667).

BP6

Variant 1-46511199-G-C is Benign according to our data. Variant chr1-46511199-G-C is described in ClinVar as [Benign]. Clinvar id is 3037813.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DMBX1	NM_172225.2 linkuse as main transcript	c.598G>C	p.Ala200Pro	missense_variant	5/6	ENST00000360032.4
DMBX1	NM_001387776.1 linkuse as main transcript	c.613G>C	p.Ala205Pro	missense_variant	4/5
DMBX1	NM_147192.4 linkuse as main transcript	c.613G>C	p.Ala205Pro	missense_variant	5/6
DMBX1	NM_001387775.1 linkuse as main transcript	c.598G>C	p.Ala200Pro	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMBX1	ENST00000360032.4 linkuse as main transcript	c.598G>C	p.Ala200Pro	missense_variant	5/6	1	NM_172225.2	P1	Q8NFW5-2

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6213

AN:

152176

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.0103

AC:

2509

AN:

244398

Hom.:

167

AF XY:

0.00764

AC XY:

1019

AN XY:

133364

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.00581

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00613

GnomAD4 exome

AF:

0.00426

AC:

6228

AN:

1461132

Hom.:

440

Cov.:

AF XY:

0.00363

AC XY:

2638

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.00709

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.00987

GnomAD4 genome

AF:

0.0408

AC:

6220

AN:

152294

Hom.:

429

Cov.:

AF XY:

0.0397

AC XY:

2956

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00601

Hom.:

Bravo

AF:

0.0462

ESP6500AA

AF:

0.114

AC:

499

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0126

AC:

1527

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DMBX1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 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

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

0.080

N;N

REVEL

Benign

0.21

Sift

Benign

0.050

D;T

Sift4G

Benign

0.30

T;T

Polyphen

0.082

B;B

Vest4

0.081

MPC

0.49

ClinPred

0.014

GERP RS

4.5

Varity_R

0.11

gMVP

0.20

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