dbSNP rs1207727: DLX6:c.437-85A>C (chr7-97007553-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005222.4(DLX6):c.437-85A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,290,700 control chromosomes in the GnomAD database, including 3,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 251 hom., cov: 33)

Exomes 𝑓: 0.067 ( 2847 hom. )

Consequence

DLX6
NM_005222.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.12

Publications

6 publications found

Variant links:

Genes affected

DLX6 (HGNC:2919): (distal-less homeobox 6) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. This family is comprised of at least 6 different members that encode proteins with roles in forebrain and craniofacial development. This gene is in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7. [provided by RefSeq, Jul 2008]

DLX6 links:

DLX6-AS1 (HGNC:37151): (DLX6 antisense RNA 1) Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DLX6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-97007553-A-C is Benign according to our data. Variant chr7-97007553-A-C is described in ClinVar as Benign. ClinVar VariationId is 1225540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4 link	c.437-85A>C		intron_variant	Intron 1 of 2	ENST00000518156.3	NP_005213.3
DLX6-AS1	NR_015448.1 link	n.141+6372T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3 link	c.437-85A>C		intron_variant	Intron 1 of 2	1	NM_005222.4	ENSP00000428480.2

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

7154

AN:

152116

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.0450

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0747

Gnomad FIN

AF:

0.0394

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0530

AC:

8219

AN:

155208

AF XY:

0.0561

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0353

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.000271

Gnomad FIN exome

AF:

0.0449

Gnomad NFE exome

AF:

0.0704

Gnomad OTH exome

AF:

0.0520

GnomAD4 exome

AF:

0.0671

AC:

76390

AN:

1138466

Hom.:

2847

Cov.:

AF XY:

0.0676

AC XY:

38775

AN XY:

573952

show subpopulations

African (AFR)

AF:

0.0127

AC:

335

AN:

26318

American (AMR)

AF:

0.0348

AC:

1237

AN:

35566

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

748

AN:

23552

East Asian (EAS)

AF:

0.000202

AC:

AN:

34730

South Asian (SAS)

AF:

0.0795

AC:

5898

AN:

74200

European-Finnish (FIN)

AF:

0.0449

AC:

2118

AN:

47152

Middle Eastern (MID)

AF:

0.0594

AC:

308

AN:

5184

European-Non Finnish (NFE)

AF:

0.0744

AC:

62684

AN:

842350

Other (OTH)

AF:

0.0618

AC:

3055

AN:

49414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4055

8110

12165

16220

20275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2144

4288

6432

8576

10720

<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:

0.0470

AC:

7155

AN:

152234

Hom.:

251

Cov.:

AF XY:

0.0453

AC XY:

3374

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0128

AC:

533

AN:

41554

American (AMR)

AF:

0.0449

AC:

687

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0756

AC:

364

AN:

4818

European-Finnish (FIN)

AF:

0.0394

AC:

418

AN:

10610

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0702

AC:

4774

AN:

67990

Other (OTH)

AF:

0.0430

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

353

706

1058

1411

1764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0531

Hom.:

Bravo

AF:

0.0458

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.6

(source)

DANN

Benign

0.82

PhyloP100

1.1

PromoterAI

-0.014

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over