Genetic Variant ARIH1:p.Gly84_Gly86del (chr15-72474873-TGGCGGCGGC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005744.5(ARIH1):c.249_257delCGGCGGCGG(p.Gly84_Gly86del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000184 in 1,413,100 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

ARIH1
NM_005744.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 4.74

Publications

1 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 -4 ACMG points.

BS2

High AC in GnomAd4 at 25 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.249_257delCGGCGGCGG	p.Gly84_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	NP_005735.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.249_257delCGGCGGCGG	p.Gly84_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000369217.4
ARIH1	ENST00000915026.1		c.249_257delCGGCGGCGG	p.Gly84_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585085.1
ARIH1	ENST00000915024.1		c.249_257delCGGCGGCGG	p.Gly84_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes

AF:

0.000167

AC:

AN:

149696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000163

Gnomad OTH

AF:

0.000488

GnomAD2 exomes

AF:

0.000454

AC:

AN:

61656

AF XY:

0.000377

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00193

Gnomad ASJ exome

AF:

0.000257

Gnomad EAS exome

AF:

0.000497

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.000639

GnomAD4 exome

AF:

0.000186

AC:

235

AN:

1263298

Hom.:

AF XY:

0.000171

AC XY:

106

AN XY:

619588

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26224

American (AMR)

AF:

0.000647

AC:

AN:

21626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20234

East Asian (EAS)

AF:

0.000144

AC:

AN:

27798

South Asian (SAS)

AF:

0.000410

AC:

AN:

58508

European-Finnish (FIN)

AF:

0.0000234

AC:

AN:

42786

Middle Eastern (MID)

AF:

0.00100

AC:

AN:

4986

European-Non Finnish (NFE)

AF:

0.000166

AC:

168

AN:

1009628

Other (OTH)

AF:

0.000311

AC:

AN:

51508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000167

AC:

AN:

149802

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

73150

show subpopulations

African (AFR)

AF:

0.0000491

AC:

AN:

40766

American (AMR)

AF:

0.000663

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5076

South Asian (SAS)

AF:

0.000214

AC:

AN:

4666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000163

AC:

AN:

67336

Other (OTH)

AF:

0.000483

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.0000583

Hom.:

Bravo

AF:

0.000181

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARIH1-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.7

Mutation Taster

=171/29

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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15-72474873-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGC

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