rs577498739
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2
The NM_001282531.3(ADNP):c.422_424dupGCA(p.Ser141dup) variant causes a conservative inframe insertion change. The variant allele was found at a frequency of 0.00388 in 1,613,890 control chromosomes in the GnomAD database, including 28 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0040 ( 27 hom. )
Consequence
ADNP
NM_001282531.3 conservative_inframe_insertion
NM_001282531.3 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.66
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001282531.3. Strenght limited to Supporting due to length of the change: 1aa.
BP6
Variant 20-50894289-G-GTGC is Benign according to our data. Variant chr20-50894289-G-GTGC is described in ClinVar as [Likely_benign]. Clinvar id is 434092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0025 (381/152314) while in subpopulation NFE AF= 0.00445 (303/68032). AF 95% confidence interval is 0.00404. There are 1 homozygotes in gnomad4. There are 172 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 381 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00250 AC: 381AN: 152196Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00230 AC: 577AN: 251090Hom.: 1 AF XY: 0.00218 AC XY: 296AN XY: 135702
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GnomAD4 exome AF: 0.00402 AC: 5878AN: 1461576Hom.: 27 Cov.: 34 AF XY: 0.00397 AC XY: 2886AN XY: 727094
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GnomAD4 genome 0.00250 AC: 381AN: 152314Hom.: 1 Cov.: 32 AF XY: 0.00231 AC XY: 172AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
| Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 08, 2019 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2025 | - - |
| Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | ADNP: PM4:Supporting, BS1, BS2 - |
ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder Benign:2
| Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
| Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not specified Benign:1
| Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 11, 2017 | - - |
Inborn genetic diseases Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2018 | This alteration is classified as likely 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 disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at