Variant summary

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

The NM_001282531.3(ADNP):c.3279C>T(p.Ala1093Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,610,974 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

ADNP
NM_001282531.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.83

Publications

2 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=-0.87).

BP6

Variant 20-50891435-G-A is Benign according to our data. Variant chr20-50891435-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.83 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000907 (138/152192) while in subpopulation NFE AF = 0.0015 (102/68040). AF 95% confidence interval is 0.00126. There are 1 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 138 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282531.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADNP	NM_001282531.3	MANE Select	c.3279C>T	p.Ala1093Ala	synonymous	Exon 6 of 6	NP_001269460.1
ADNP	NM_001439000.1		c.3495C>T	p.Ala1165Ala	synonymous	Exon 6 of 6	NP_001425929.1
ADNP	NM_001282532.2		c.3279C>T	p.Ala1093Ala	synonymous	Exon 4 of 4	NP_001269461.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADNP	ENST00000621696.5	TSL:5 MANE Select	c.3279C>T	p.Ala1093Ala	synonymous	Exon 6 of 6	ENSP00000483881.1
ADNP	ENST00000349014.8	TSL:1	c.3279C>T	p.Ala1093Ala	synonymous	Exon 4 of 4	ENSP00000342905.3
ADNP	ENST00000371602.9	TSL:1	c.3279C>T	p.Ala1093Ala	synonymous	Exon 3 of 3	ENSP00000360662.2

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000899

AC:

223

AN:

248066

AF XY:

0.000835

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.000552

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.000147

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00189

AC:

2753

AN:

1458782

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1313

AN XY:

725706

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33446

American (AMR)

AF:

0.000516

AC:

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000268

AC:

AN:

85936

European-Finnish (FIN)

AF:

0.000212

AC:

AN:

51804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00235

AC:

2612

AN:

1111222

Other (OTH)

AF:

0.00118

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

172

344

515

687

859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.000907

AC:

138

AN:

152192

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

41448

American (AMR)

AF:

0.000458

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00150

AC:

102

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00107

EpiCase

AF:

0.00131

EpiControl

AF:

0.00184

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ADNP-related disorder (1)

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.38

(source)

DANN

Benign

0.35

PhyloP100

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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.

rs142247083

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over