NM_021008.4:c.1401G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021008.4(DEAF1):c.1401G>A(p.Ala467Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,614,138 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 34 hom., cov: 33)

Exomes 𝑓: 0.019 ( 502 hom. )

Consequence

DEAF1
NM_021008.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.78

Publications

6 publications found

Variant links:

Genes affected

DEAF1 (HGNC:14677): (DEAF1 transcription factor) This gene encodes a zinc finger domain-containing protein that functions as a regulator of transcription. The encoded proteins binds to its own promoter as well as to that of several target genes. Activity of this protein is important in the regulation of embryonic development. Mutations in this gene have been found in individuals with autosomal dominant cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DEAF1 Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 24
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
intellectual disability-epilepsy-extrapyramidal syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
complex neurodevelopmental disorder
Inheritance: SD Classification: STRONG Submitted by: Illumina
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DEAF1 links:

ENSG00000255158 (HGNC:):

ENSG00000255158 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 11-674638-C-T is Benign according to our data. Variant chr11-674638-C-T is described in ClinVar as Benign. ClinVar VariationId is 585771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.78 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEAF1	NM_021008.4 link	c.1401G>A	p.Ala467Ala	synonymous_variant	Exon 10 of 12	ENST00000382409.4	NP_066288.2	O75398-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEAF1	ENST00000382409.4 link	c.1401G>A	p.Ala467Ala	synonymous_variant	Exon 10 of 12	1	NM_021008.4	ENSP00000371846.3		O75398-1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2198

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0550

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0208

AC:

5240

AN:

251460

AF XY:

0.0244

show subpopulations

Gnomad AFR exome

AF:

0.00369

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.0428

Gnomad EAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.00264

Gnomad NFE exome

AF:

0.0162

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0193

AC:

28244

AN:

1461812

Hom.:

502

Cov.:

AF XY:

0.0210

AC XY:

15238

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00394

AC:

132

AN:

33480

American (AMR)

AF:

0.0133

AC:

595

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0394

AC:

1030

AN:

26136

East Asian (EAS)

AF:

0.00831

AC:

330

AN:

39700

South Asian (SAS)

AF:

0.0656

AC:

5658

AN:

86258

European-Finnish (FIN)

AF:

0.00279

AC:

149

AN:

53342

Middle Eastern (MID)

AF:

0.0517

AC:

298

AN:

5768

European-Non Finnish (NFE)

AF:

0.0168

AC:

18658

AN:

1112008

Other (OTH)

AF:

0.0231

AC:

1394

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1878

3756

5633

7511

9389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.0144

AC:

2196

AN:

152326

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1090

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00440

AC:

183

AN:

41572

American (AMR)

AF:

0.0180

AC:

276

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3472

East Asian (EAS)

AF:

0.0152

AC:

AN:

5186

South Asian (SAS)

AF:

0.0547

AC:

264

AN:

4830

European-Finnish (FIN)

AF:

0.00226

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0171

AC:

1160

AN:

68030

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

111

222

332

443

554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0170

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0179

EpiControl

AF:

0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 02, 2024

Athena Diagnostics

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

-0.69

CADD

Benign

0.093

(source)

DANN

Benign

0.81

PhyloP100

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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