rs761240

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-50891355-T-G
• chr20-50891355-T-A
• chr20-50891355-T-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
• Publications: 11 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 -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 VariationId 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.

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.*50A>C		3_prime_UTR	Exon 6 of 6	NP_001269460.1	Q9H2P0
	ADNP	NM_001439000.1		c.*50A>C		3_prime_UTR	Exon 6 of 6	NP_001425929.1
	ADNP	NM_001282532.2		c.*50A>C		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.*50A>C		3_prime_UTR	Exon 6 of 6	ENSP00000483881.1	Q9H2P0
	ADNP	ENST00000349014.8	TSL:1	c.*50A>C		3_prime_UTR	Exon 4 of 4	ENSP00000342905.3	Q9H2P0
	ADNP	ENST00000371602.9	TSL:1	c.*50A>C		3_prime_UTR	Exon 3 of 3	ENSP00000360662.2	Q9H2P0

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

African (AFR) AF: 0.988 AC: 30491 AN: 30872

American (AMR) AF: 0.965 AC: 30743 AN: 31866

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 19223 AN: 21052

East Asian (EAS) AF: 1.00 AC: 38057 AN: 38066

South Asian (SAS) AF: 0.929 AC: 66899 AN: 72002

European-Finnish (FIN) AF: 0.948 AC: 37647 AN: 39704

Middle Eastern (MID) AF: 0.892 AC: 4634 AN: 5196

European-Non Finnish (NFE) AF: 0.926 AC: 992483 AN: 1072144

Other (OTH) 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

African (AFR) AF: 0.987 AC: 41050 AN: 41588

American (AMR) AF: 0.955 AC: 14614 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5171 AN: 5174

South Asian (SAS) AF: 0.932 AC: 4498 AN: 4828

European-Finnish (FIN) AF: 0.953 AC: 10126 AN: 10620

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63074 AN: 68030

Other (OTH) AF: 0.939 AC: 1986 AN: 2114

Alfa AF: 0.933 Hom.: 93451

Bravo AF: 0.952

Asia WGS AF: 0.976 AC: 3393 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.65
PhyloP100		0.081
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

Other links and lift over

dbSNP: rs761240; hg19: chr20-49507892;