20-50891355-T-G

Variant names:

• chr20-50891355-T-G
• rs761240
• NM_001282531.3:c.*50A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282531.3(ADNP):​c.*50A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,520,046 control chromosomes in the GnomAD database, including 661,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68907 hom., cov: 34)
  • Exomes 𝑓: 0.93 (592966 hom.)
• Consequence: ADNP NM_001282531.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0810

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-50891355-T-G is Benign according to our data. Variant chr20-50891355-T-G is described in ClinVar as [Benign]. Clinvar id is 1189012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADNP	NM_001282531.3	c.*50A>C		3_prime_UTR_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	c.*50A>C		3_prime_UTR_variant	Exon 6 of 6	5	NM_001282531.3	ENSP00000483881.1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144697 AN: 152224 Hom.: 68845 Cov.: 34

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.939

GnomAD2 exomes AF: 0.946 AC: 145586 AN: 153852 AF XY: 0.942

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.968

Gnomad ASJ exome AF: 0.910

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.949

Gnomad NFE exome AF: 0.927

Gnomad OTH exome AF: 0.940

GnomAD4 exome AF: 0.931 AC: 1273189 AN: 1367704 Hom.: 592966 Cov.: 61 AF XY: 0.931 AC XY: 626263 AN XY: 672884

Gnomad4 AFR exome AF: 0.988 AC: 30491 AN: 30872

Gnomad4 AMR exome AF: 0.965 AC: 30743 AN: 31866

Gnomad4 ASJ exome AF: 0.913 AC: 19223 AN: 21052

Gnomad4 EAS exome AF: 1.00 AC: 38057 AN: 38066

Gnomad4 SAS exome AF: 0.929 AC: 66899 AN: 72002

Gnomad4 FIN exome AF: 0.948 AC: 37647 AN: 39704

Gnomad4 NFE exome AF: 0.926 AC: 992483 AN: 1072144

Gnomad4 Remaining exome AF: 0.933 AC: 53012 AN: 56802

GnomAD4 genome AF: 0.951 AC: 144818 AN: 152342 Hom.: 68907 Cov.: 34 AF XY: 0.951 AC XY: 70866 AN XY: 74486

Gnomad4 AFR AF: 0.987 AC: 0.987064 AN: 0.987064

Gnomad4 AMR AF: 0.955 AC: 0.95454 AN: 0.95454

Gnomad4 ASJ AF: 0.920 AC: 0.919643 AN: 0.919643

Gnomad4 EAS AF: 0.999 AC: 0.99942 AN: 0.99942

Gnomad4 SAS AF: 0.932 AC: 0.931649 AN: 0.931649

Gnomad4 FIN AF: 0.953 AC: 0.953484 AN: 0.953484

Gnomad4 NFE AF: 0.927 AC: 0.92715 AN: 0.92715

Gnomad4 OTH AF: 0.939 AC: 0.939451 AN: 0.939451

Alfa AF: 0.933 Hom.: 93451

Bravo AF: 0.952

Asia WGS AF: 0.976 AC: 3393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761240; hg19: chr20-49507892;