rs2295343

Positions:

• chr20-3754954-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258429.2(ADISSP):​c.302-435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,954 control chromosomes in the GnomAD database, including 14,502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (14502 hom., cov: 31)
• Consequence: ADISSP NM_001258429.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

ADISSP (HGNC:15873): (adipose secreted signaling protein) Enables protein phosphatase 1 binding activity. Involved in positive regulation of NIK/NF-kappaB signaling and positive regulation of transforming growth factor beta receptor signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADISSP	NM_001258429.2	c.302-435T>C		intron_variant		ENST00000379772.4	NP_001245358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADISSP	ENST00000379772.4	c.302-435T>C		intron_variant		1	NM_001258429.2	ENSP00000369097	P1
ADISSP	ENST00000217195.12	c.377-435T>C		intron_variant		2		ENSP00000217195
ADISSP	ENST00000399672.5	c.302-435T>C		intron_variant		2		ENSP00000382580	P1
ADISSP	ENST00000399683.7	c.282+515T>C		intron_variant		2		ENSP00000382591

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64496 AN: 151836 Hom.: 14477 Cov.: 31

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.425 AC: 64569 AN: 151954 Hom.: 14502 Cov.: 31 AF XY: 0.422 AC XY: 31318 AN XY: 74288

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.372

Alfa AF: 0.388 Hom.: 16675

Bravo AF: 0.422

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295343; hg19: chr20-3735601; COSMIC: COSV53923810; COSMIC: COSV53923810;