Variant 20-50892146-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001282531.3(ADNP):c.2568C>T(p.Val856=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ADNP	NM_001282531.3 linkuse as main transcript	c.2568C>T	p.Val856=	synonymous_variant	6/6	ENST00000621696.5	NP_001269460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADNP	ENST00000621696.5 linkuse as main transcript	c.2568C>T	p.Val856=	synonymous_variant	6/6	5	NM_001282531.3	ENSP00000483881	P1

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

GnomAD3 exomes

AF:

0.0369

AC:

9260

AN:

251074

Hom.:

759

AF XY:

0.0321

AC XY:

4349

AN XY:

135682

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 SAS exome

AF:

0.0291

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

Gnomad4 AFR exome

AF:

0.309

Gnomad4 AMR exome

AF:

0.0278

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0144

Gnomad4 SAS exome

AF:

0.0277

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0365

GnomAD4 genome

AF:

0.0947

AC:

14403

AN:

152134

Hom.:

1849

Cov.:

AF XY:

0.0917

AC XY:

6820

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.0404

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0188

Gnomad4 SAS

AF:

0.0317

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.0742

Alfa

AF:

0.0297

Hom.:

641

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2016

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.2

DANN

Benign

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over