Genetic Variant NM_021008.4:c.882C>G (chr11-681078-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021008.4(DEAF1):c.882C>G(p.Val294Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,614,090 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V294V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0075 ( 3 hom., cov: 32)

Exomes 𝑓: 0.010 ( 97 hom. )

Consequence

DEAF1
NM_021008.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.442

Publications

1 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, Ambry Genetics, Orphanet
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:

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=-0.48).

BP6

Variant 11-681078-G-C is Benign according to our data. Variant chr11-681078-G-C is described in ClinVar as Benign. ClinVar VariationId is 585777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.442 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00748 (1139/152276) while in subpopulation NFE AF = 0.0112 (764/68022). AF 95% confidence interval is 0.0106. There are 3 homozygotes in GnomAd4. There are 501 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021008.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEAF1	NM_021008.4	MANE Select	c.882C>G	p.Val294Val	synonymous	Exon 7 of 12	NP_066288.2
DEAF1	NM_001440883.1		c.882C>G	p.Val294Val	synonymous	Exon 7 of 11	NP_001427812.1
DEAF1	NM_001440884.1		c.882C>G	p.Val294Val	synonymous	Exon 7 of 11	NP_001427813.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEAF1	ENST00000382409.4	TSL:1 MANE Select	c.882C>G	p.Val294Val	synonymous	Exon 7 of 12	ENSP00000371846.3	O75398-1
DEAF1	ENST00000527170.5	TSL:1	n.243C>G		non_coding_transcript_exon	Exon 4 of 10	ENSP00000431563.1	H0YCH1
DEAF1	ENST00000882097.1		c.1008C>G	p.Val336Val	synonymous	Exon 8 of 13	ENSP00000552156.1

Frequencies

GnomAD3 genomes

AF:

0.00748

AC:

1138

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00843

AC:

2119

AN:

251480

AF XY:

0.00853

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00517

Gnomad ASJ exome

AF:

0.0334

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00700

GnomAD4 exome

AF:

0.00997

AC:

14578

AN:

1461814

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

7274

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33478

American (AMR)

AF:

0.00584

AC:

261

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0307

AC:

802

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00245

AC:

211

AN:

86248

European-Finnish (FIN)

AF:

0.00386

AC:

206

AN:

53418

Middle Eastern (MID)

AF:

0.00857

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0111

AC:

12386

AN:

1112004

Other (OTH)

AF:

0.0103

AC:

620

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

910

1821

2731

3642

4552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.00748

AC:

1139

AN:

152276

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

501

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41538

American (AMR)

AF:

0.00804

AC:

123

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

124

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00270

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

764

AN:

68022

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0130

Hom.:

Bravo

AF:

0.00856

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0138

EpiControl

AF:

0.0154

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.7

(source)

DANN

Benign

0.78

PhyloP100

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over