Genetic Variant ARPP21:c.2137+151G>A (chr3-35744116-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001385562.1(ARPP21):c.2137+151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 794,540 control chromosomes in the GnomAD database, including 4,721 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 0.10 ( 831 hom., cov: 32)

Exomes 𝑓: 0.10 ( 3890 hom. )

Consequence

ARPP21
NM_001385562.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.251

Publications

7 publications found

Variant links:

Genes affected

ARPP21 (HGNC:16968): (cAMP regulated phosphoprotein 21) This gene encodes a cAMP-regulated phosphoprotein. The encoded protein is enriched in the caudate nucleus and cerebellar cortex. A similar protein in mouse may be involved in regulating the effects of dopamine in the basal ganglia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ARPP21 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ARPP21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPP21	NM_001385562.1 link	c.2137+151G>A		intron_variant	Intron 19 of 20	ENST00000684406.1	NP_001372491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPP21	ENST00000684406.1 link	c.2137+151G>A		intron_variant	Intron 19 of 20		NM_001385562.1	ENSP00000506922.1		A0A804HI65

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15460

AN:

152128

Hom.:

832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0833

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0966

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0695

Gnomad SAS

AF:

0.0673

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.0761

GnomAD4 exome

AF:

0.103

AC:

66126

AN:

642294

Hom.:

3890

AF XY:

0.102

AC XY:

34181

AN XY:

333864

show subpopulations

African (AFR)

AF:

0.0793

AC:

1324

AN:

16704

American (AMR)

AF:

0.104

AC:

2577

AN:

24866

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

1959

AN:

15376

East Asian (EAS)

AF:

0.0581

AC:

1941

AN:

33396

South Asian (SAS)

AF:

0.0697

AC:

3729

AN:

53508

European-Finnish (FIN)

AF:

0.0854

AC:

3677

AN:

43054

Middle Eastern (MID)

AF:

0.0481

AC:

153

AN:

3178

European-Non Finnish (NFE)

AF:

0.113

AC:

47564

AN:

419854

Other (OTH)

AF:

0.0990

AC:

3202

AN:

32358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2894

5788

8681

11575

14469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.102

AC:

15459

AN:

152246

Hom.:

831

Cov.:

AF XY:

0.0989

AC XY:

7361

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0832

AC:

3456

AN:

41532

American (AMR)

AF:

0.0964

AC:

1475

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

449

AN:

3468

East Asian (EAS)

AF:

0.0691

AC:

358

AN:

5180

South Asian (SAS)

AF:

0.0667

AC:

322

AN:

4828

European-Finnish (FIN)

AF:

0.0867

AC:

920

AN:

10610

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8213

AN:

68016

Other (OTH)

AF:

0.0754

AC:

159

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

706

1413

2119

2826

3532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.113

Hom.:

2759

Bravo

AF:

0.102

Asia WGS

AF:

0.0810

AC:

284

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.1

(source)

DANN

Benign

0.80

PhyloP100

0.25

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