20-50891414-T-C

Variant names:

• chr20-50891414-T-C
• rs1274995389
• NM_001282531.3:c.3300A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001282531.3(ADNP):​c.3300A>G​(p.Gln1100Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 1,604,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: ADNP NM_001282531.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.332
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-50891414-T-C is Benign according to our data. Variant chr20-50891414-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2993454.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.332 with no splicing effect.
• BS2: High AC in GnomAd4 at 11 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.3300A>G	p.Gln1100Gln	synonymous	Exon 6 of 6	NP_001269460.1	Q9H2P0
	ADNP	NM_001439000.1		c.3516A>G	p.Gln1172Gln	synonymous	Exon 6 of 6	NP_001425929.1
	ADNP	NM_001282532.2		c.3300A>G	p.Gln1100Gln	synonymous	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.3300A>G	p.Gln1100Gln	synonymous	Exon 6 of 6	ENSP00000483881.1	Q9H2P0
	ADNP	ENST00000349014.8	TSL:1	c.3300A>G	p.Gln1100Gln	synonymous	Exon 4 of 4	ENSP00000342905.3	Q9H2P0
	ADNP	ENST00000371602.9	TSL:1	c.3300A>G	p.Gln1100Gln	synonymous	Exon 3 of 3	ENSP00000360662.2	Q9H2P0

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000827 AC: 2 AN: 241810 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000248 AC: 36 AN: 1451674 Hom.: 0 Cov.: 35 AF XY: 0.0000263 AC XY: 19 AN XY: 721682

African (AFR) AF: 0.0000300 AC: 1 AN: 33280

American (AMR) AF: 0.0000227 AC: 1 AN: 43966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25500

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 84656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000235 AC: 26 AN: 1107984

Other (OTH) AF: 0.000133 AC: 8 AN: 60010

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152370 Hom.: 1 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74514

African (AFR) AF: 0.0000721 AC: 3 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000378

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	-0.86
CADD	Benign	0.41
DANN	Benign	0.25
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs1274995389; hg19: chr20-49507951;