rs1062651

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001282531.3(ADNP):c.2568C>T(p.Val856Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,613,998 control chromosomes in the GnomAD database, including 3,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 1849 hom., cov: 33)

Exomes 𝑓: 0.023 ( 1915 hom. )

Consequence

ADNP
NM_001282531.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.48

Publications

11 publications found

Variant links:

Genes affected

ADNP (HGNC:15766): (activity dependent neuroprotector homeobox) Vasoactive intestinal peptide is a neuroprotective factor that has a stimulatory effect on the growth of some tumor cells and an inhibitory effect on others. This gene encodes a protein that is upregulated by vasoactive intestinal peptide and may be involved in its stimulatory effect on certain tumor cells. The encoded protein contains one homeobox and nine zinc finger domains, suggesting that it functions as a transcription factor. This gene is also upregulated in normal proliferative tissues. Finally, the encoded protein may increase the viability of certain cell types through modulation of p53 activity. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ADNP Gene-Disease associations (from GenCC):

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder
Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ADNP 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=-0.66).

BP6

Variant 20-50892146-G-A is Benign according to our data. Variant chr20-50892146-G-A is described in ClinVar as Benign. ClinVar VariationId is 587839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADNP	NM_001282531.3 link	c.2568C>T	p.Val856Val	synonymous_variant	Exon 6 of 6	ENST00000621696.5	NP_001269460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADNP	ENST00000621696.5 link	c.2568C>T	p.Val856Val	synonymous_variant	Exon 6 of 6	5	NM_001282531.3	ENSP00000483881.1

Frequencies

GnomAD3 genomes

AF:

0.0945

AC:

14365

AN:

152016

Hom.:

1837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.0321

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.0745

GnomAD2 exomes

AF:

0.0369

AC:

9260

AN:

251074

AF XY:

0.0321

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.0242

Gnomad ASJ exome

AF:

0.0204

Gnomad EAS exome

AF:

0.0213

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0227

AC:

33114

AN:

1461864

Hom.:

1915

Cov.:

AF XY:

0.0218

AC XY:

15845

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.309

AC:

10338

AN:

33478

American (AMR)

AF:

0.0278

AC:

1245

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

494

AN:

26136

East Asian (EAS)

AF:

0.0144

AC:

572

AN:

39700

South Asian (SAS)

AF:

0.0277

AC:

2392

AN:

86254

European-Finnish (FIN)

AF:

0.0122

AC:

651

AN:

53400

Middle Eastern (MID)

AF:

0.0293

AC:

169

AN:

5768

European-Non Finnish (NFE)

AF:

0.0135

AC:

15050

AN:

1112008

Other (OTH)

AF:

0.0365

AC:

2203

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1867

3734

5601

7468

9335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.0947

AC:

14403

AN:

152134

Hom.:

1849

Cov.:

AF XY:

0.0917

AC XY:

6820

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.291

AC:

12073

AN:

41444

American (AMR)

AF:

0.0404

AC:

617

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3472

East Asian (EAS)

AF:

0.0188

AC:

AN:

5168

South Asian (SAS)

AF:

0.0317

AC:

153

AN:

4820

European-Finnish (FIN)

AF:

0.0151

AC:

160

AN:

10604

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0157

AC:

1068

AN:

68016

Other (OTH)

AF:

0.0742

AC:

157

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

540

1079

1619

2158

2698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0456

Hom.:

2139

Bravo

AF:

0.105

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

EpiCase

AF:

0.0134

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 15, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

Benign:1

Dec 05, 2021

Genome-Nilou Lab

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

-0.66

CADD

Benign

2.2

(source)

DANN

Benign

0.52

PhyloP100

1.5

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over