Variant chr17-49973193-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138281.3(DLX4):c.404G>C(p.Arg135Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00411 in 1,614,134 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 13 hom. )

Consequence

DLX4
NM_138281.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.74

Variant links:

Genes affected

DLX4 (HGNC:2917): (distal-less homeobox 4) Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. The DLX proteins are postulated to play a role in forebrain and craniofacial development. Three transcript variants have been described for this gene, however, the full length nature of one variant has not been described. Studies of the two splice variants revealed that one encoded isoform functions as a repressor of the beta-globin gene while the other isoform lacks that function. [provided by RefSeq, Jul 2008]

DLX4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02380076).

BP6

Variant 17-49973193-G-C is Benign according to our data. Variant chr17-49973193-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 788750.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 430 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX4	NM_138281.3 link	c.404G>C	p.Arg135Pro	missense_variant	2/3	ENST00000240306.5	NP_612138.1	Q92988-1
DLX4	NM_001934.4 link	c.188G>C	p.Arg63Pro	missense_variant	1/2		NP_001925.2	Q92988-2
DLX4	XM_047435517.1 link	c.188G>C	p.Arg63Pro	missense_variant	2/3		XP_047291473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX4	ENST00000240306.5 link	c.404G>C	p.Arg135Pro	missense_variant	2/3	1	NM_138281.3	ENSP00000240306.3		Q92988-1

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

430

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00460

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00263

AC:

660

AN:

250948

Hom.:

AF XY:

0.00266

AC XY:

361

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.000866

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00384

Gnomad NFE exome

AF:

0.00462

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00425

AC:

6210

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

3023

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00360

Gnomad4 NFE exome

AF:

0.00525

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00282

AC:

430

AN:

152270

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00460

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00319

Hom.:

Bravo

AF:

0.00251

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00272

AC:

330

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DLX4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Pathogenic

0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;.;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.4

M;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-6.3

D;D;.

REVEL

Pathogenic

0.82

Sift

Uncertain

0.0010

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.75

MVP

0.99

MPC

1.0

ClinPred

0.048

GERP RS

3.9

Varity_R

0.87

gMVP

0.82

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