20-50892146-G-A

Variant names:

• chr20-50892146-G-A
• rs1062651
• NM_001282531.3:c.2568C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.48

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ADNP	NM_001282531.3	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	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.: 33

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

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.: 35 AF XY: 0.0218 AC XY: 15845 AN XY: 727232

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.: 33 AF XY: 0.0917 AC XY: 6820 AN XY: 74388

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

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
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

Other links and lift over

dbSNP: rs1062651; hg19: chr20-49508683; COSMIC: COSV62426339; COSMIC: COSV62426339;