Genetic Variant ADISSP:c.*191A>G (chr20-3753867-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001258429.2(ADISSP):c.*191A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 597,928 control chromosomes in the GnomAD database, including 33,247 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 0.30 ( 7285 hom., cov: 33)

Exomes 𝑓: 0.33 ( 25962 hom. )

Consequence

ADISSP
NM_001258429.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247

Publications

10 publications found

Variant links:

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]

ADISSP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADISSP	NM_001258429.2 link	c.*191A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000379772.4	NP_001245358.1	Q9GZN8-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADISSP	ENST00000379772.4 link	c.*191A>G	3_prime_UTR_variant	Exon 6 of 6	1	NM_001258429.2	ENSP00000369097.4	Q9GZN8-1
ADISSP	ENST00000217195.12 link	c.*191A>G	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000217195.8	Q9GZN8-2
ADISSP	ENST00000399672.5 link	c.*191A>G	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000382580.1	Q9GZN8-1
ADISSP	ENST00000399683.7 link	c.*191A>G	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000382591.3	H7BYU9

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45001

AN:

150594

Hom.:

7279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.335

AC:

149605

AN:

447214

Hom.:

25962

Cov.:

AF XY:

0.333

AC XY:

78693

AN XY:

236154

show subpopulations

African (AFR)

AF:

0.182

AC:

2209

AN:

12148

American (AMR)

AF:

0.328

AC:

6362

AN:

19370

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

3874

AN:

13630

East Asian (EAS)

AF:

0.169

AC:

5093

AN:

30110

South Asian (SAS)

AF:

0.327

AC:

15123

AN:

46180

European-Finnish (FIN)

AF:

0.422

AC:

12576

AN:

29814

Middle Eastern (MID)

AF:

0.287

AC:

1028

AN:

3580

European-Non Finnish (NFE)

AF:

0.357

AC:

94995

AN:

266426

Other (OTH)

AF:

0.322

AC:

8345

AN:

25956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4797

9593

14390

19186

23983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

45027

AN:

150714

Hom.:

7285

Cov.:

AF XY:

0.302

AC XY:

22228

AN XY:

73694

show subpopulations

African (AFR)

AF:

0.179

AC:

7322

AN:

40852

American (AMR)

AF:

0.318

AC:

4825

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

939

AN:

3456

East Asian (EAS)

AF:

0.166

AC:

841

AN:

5070

South Asian (SAS)

AF:

0.316

AC:

1505

AN:

4758

European-Finnish (FIN)

AF:

0.425

AC:

4453

AN:

10468

Middle Eastern (MID)

AF:

0.276

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.359

AC:

24261

AN:

67626

Other (OTH)

AF:

0.269

AC:

564

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1621

3241

4862

6482

8103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.325

Hom.:

3187

Bravo

AF:

0.283

Asia WGS

AF:

0.207

AC:

720

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over