Genetic Variant ARIH1:p.Glu15Gly (chr15-72474683-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_005744.5(ARIH1):c.44A>G(p.Glu15Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000562 in 1,422,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E15Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

ARIH1
NM_005744.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.52

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3022403).

BS2

High AC in GnomAdExome4 at 8 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.44A>G	p.Glu15Gly	missense	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.44A>G	p.Glu15Gly	missense	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
ARIH1	ENST00000915026.1		c.44A>G	p.Glu15Gly	missense	Exon 1 of 14	ENSP00000585085.1
ARIH1	ENST00000915024.1		c.44A>G	p.Glu15Gly	missense	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

204504

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000562

AC:

AN:

1422944

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

707248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30156

American (AMR)

AF:

0.00

AC:

AN:

40034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24972

East Asian (EAS)

AF:

0.00

AC:

AN:

35404

South Asian (SAS)

AF:

0.00

AC:

AN:

82006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00000731

AC:

AN:

1094206

Other (OTH)

AF:

0.00

AC:

AN:

58678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.30

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

0.34

PhyloP100

5.5

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.39

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

Sift4G

Benign

0.087

Polyphen

0.66

Vest4

0.27

MutPred

0.13

Loss of solvent accessibility (P = 0.0187)

MVP

0.64

MPC

1.2

ClinPred

0.80

GERP RS

3.8

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.50

gMVP

0.15

Mutation Taster

=42/58

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over