Genetic Variant ARIH1:p.Glu20del (chr15-72474693-TGAG-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005744.5(ARIH1):c.60_62delGGA(p.Glu20del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000444 in 1,570,930 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 11 hom. )

Consequence

ARIH1
NM_005744.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.01

Publications

0 publications found

Variant links:

Genes affected

ARIH1 (HGNC:689): (ariadne RBR E3 ubiquitin protein ligase 1) Enables enzyme binding activity; ubiquitin-protein transferase activity; and zinc ion binding activity. Involved in protein ubiquitination. Located in Lewy body; cytoplasm; and nuclear body. Colocalizes with cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ARIH1 links:

TMEM202-AS1 (HGNC:53265): (TMEM202 antisense RNA 1)

TMEM202-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 15-72474693-TGAG-T is Benign according to our data. Variant chr15-72474693-TGAG-T is described in ClinVar as Benign. ClinVar VariationId is 1658666.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 32 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005744.5. 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
	ARIH1	NM_005744.5	MANE Select	c.60_62delGGA	p.Glu20del	disruptive_inframe_deletion	Exon 1 of 14	NP_005735.2	Q9Y4X5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.60_62delGGA	p.Glu20del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
ARIH1	ENST00000915026.1		c.60_62delGGA	p.Glu20del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585085.1
ARIH1	ENST00000915024.1		c.60_62delGGA	p.Glu20del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes

AF:

0.000218

AC:

AN:

151362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00562

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.000962

GnomAD2 exomes

AF:

0.000929

AC:

191

AN:

205606

AF XY:

0.00127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000503

Gnomad NFE exome

AF:

0.0000428

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.000468

AC:

665

AN:

1419460

Hom.:

AF XY:

0.000656

AC XY:

463

AN XY:

705880

show subpopulations

African (AFR)

AF:

0.0000334

AC:

AN:

29918

American (AMR)

AF:

0.000126

AC:

AN:

39744

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24774

East Asian (EAS)

AF:

0.0000576

AC:

AN:

34732

South Asian (SAS)

AF:

0.00714

AC:

583

AN:

81664

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52182

Middle Eastern (MID)

AF:

0.000535

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.0000412

AC:

AN:

1092396

Other (OTH)

AF:

0.000428

AC:

AN:

58446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000211

AC:

AN:

151470

Hom.:

Cov.:

AF XY:

0.000284

AC XY:

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41338

American (AMR)

AF:

0.0000656

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00563

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

67784

Other (OTH)

AF:

0.000476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000214

Hom.:

Bravo

AF:

0.0000907

Asia WGS

AF:

0.00234

AC:

AN:

3436

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.0

Mutation Taster

=72/28

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over