Genetic Variant DLX4:c.*465C>T (chr17-49974408-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138281.3(DLX4):c.*465C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,260 control chromosomes in the GnomAD database, including 3,464 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 0.21 ( 3456 hom., cov: 31)

Exomes 𝑓: 0.21 ( 8 hom. )

Consequence

DLX4
NM_138281.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0590

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

orofacial cleft 15
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

DLX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DLX4	NM_138281.3 link	c.*465C>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000240306.5	NP_612138.1	Q92988-1
DLX4	NM_001934.4 link	c.*465C>T	3_prime_UTR_variant	Exon 2 of 2		NP_001925.2	Q92988-2
DLX4	XM_047435517.1 link	c.*465C>T	3_prime_UTR_variant	Exon 3 of 3		XP_047291473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX4	ENST00000240306.5 link	c.*465C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_138281.3	ENSP00000240306.3		Q92988-1

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31914

AN:

151714

Hom.:

3452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.207

AC:

AN:

430

Hom.:

Cov.:

AF XY:

0.229

AC XY:

AN XY:

210

show subpopulations

African (AFR)

AF:

0.308

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.350

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.185

AC:

AN:

286

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.210

AC:

31930

AN:

151830

Hom.:

3456

Cov.:

AF XY:

0.211

AC XY:

15642

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.237

AC:

9818

AN:

41384

American (AMR)

AF:

0.137

AC:

2084

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

644

AN:

3468

East Asian (EAS)

AF:

0.241

AC:

1243

AN:

5156

South Asian (SAS)

AF:

0.298

AC:

1429

AN:

4800

European-Finnish (FIN)

AF:

0.207

AC:

2184

AN:

10538

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13854

AN:

67916

Other (OTH)

AF:

0.195

AC:

409

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1243

2486

3730

4973

6216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

6233

Bravo

AF:

0.204

Asia WGS

AF:

0.234

AC:

817

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

(source)

DANN

Benign

0.46

PhyloP100

0.059

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over