NM_001282531.3:c.*1576G>A

Variant names:

• chr20-50889829-C-T
• rs565387781
• NM_001282531.3:c.*1576G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001282531.3(ADNP):​c.*1576G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 398,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00086 (0 hom.)
• Consequence: ADNP NM_001282531.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

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, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-50889829-C-T is Benign according to our data. Variant chr20-50889829-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2652398.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000644 (98/152276) while in subpopulation NFE AF = 0.00116 (79/68034). AF 95% confidence interval is 0.000954. There are 0 homozygotes in GnomAd4. There are 43 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 98 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADNP	NM_001282531.3	MANE Select	c.*1576G>A		3_prime_UTR	Exon 6 of 6	NP_001269460.1	Q9H2P0
	ADNP	NM_001439000.1		c.*1576G>A		3_prime_UTR	Exon 6 of 6	NP_001425929.1
	ADNP	NM_001282532.2		c.*1576G>A		3_prime_UTR	Exon 4 of 4	NP_001269461.1	Q9H2P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADNP	ENST00000621696.5	TSL:5 MANE Select	c.*1576G>A		3_prime_UTR	Exon 6 of 6	ENSP00000483881.1	Q9H2P0
	ADNP	ENST00000371602.9	TSL:1	c.*1576G>A		3_prime_UTR	Exon 3 of 3	ENSP00000360662.2	Q9H2P0
	ADNP	ENST00000396029.8	TSL:1	c.*1576G>A		3_prime_UTR	Exon 5 of 5	ENSP00000379346.3	Q9H2P0

Frequencies

GnomAD3 genomes AF: 0.000637 AC: 97 AN: 152158 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000857 AC: 211 AN: 246240 Hom.: 0 Cov.: 0 AF XY: 0.000938 AC XY: 117 AN XY: 124762

African (AFR) AF: 0.00 AC: 0 AN: 7180

American (AMR) AF: 0.000269 AC: 2 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.000108 AC: 1 AN: 9238

East Asian (EAS) AF: 0.00 AC: 0 AN: 22890

South Asian (SAS) AF: 0.000330 AC: 1 AN: 3032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1292

European-Non Finnish (NFE) AF: 0.00120 AC: 189 AN: 157990

Other (OTH) AF: 0.00110 AC: 18 AN: 16368

GnomAD4 genome AF: 0.000644 AC: 98 AN: 152276 Hom.: 0 Cov.: 31 AF XY: 0.000578 AC XY: 43 AN XY: 74444

African (AFR) AF: 0.000217 AC: 9 AN: 41540

American (AMR) AF: 0.000588 AC: 9 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000693 Hom.: 0

Bravo AF: 0.000691

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.59
PhyloP100		1.6
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs565387781; hg19: chr20-49506366;