Variant chr15-72474711-CGAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_005744.5(ARIH1):c.84_86delGGA(p.Glu28del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,558,990 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

ARIH1
NM_005744.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.77

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 15-72474711-CGAG-C is Benign according to our data. Variant chr15-72474711-CGAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 1556148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARIH1	NM_005744.5 link	c.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	1/14	ENST00000379887.9	NP_005735.2	Q9Y4X5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARIH1	ENST00000379887.9 link	c.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	1/14	1	NM_005744.5	ENSP00000369217.4	Q9Y4X5
ARIH1	ENST00000564062.1 link	c.78_80delGGA	p.Glu26del	disruptive_inframe_deletion	1/4	3		ENSP00000454774.1	H3BNB9
TMEM202-AS1	ENST00000565181.1 link	n.455_457delCTC		non_coding_transcript_exon_variant	1/1	6
ARIH1	ENST00000570085.5 link	n.84_86delGGA		non_coding_transcript_exon_variant	1/5	3		ENSP00000456746.1	H3BSK4

Frequencies

GnomAD3 genomes

AF:

0.000724

AC:

110

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000759

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000942

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00130

AC:

1831

AN:

1406978

Hom.:

AF XY:

0.00128

AC XY:

898

AN XY:

699658

show subpopulations

Gnomad4 AFR exome

AF:

0.000884

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00794

Gnomad4 EAS exome

AF:

0.00101

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.00171

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.000724

AC:

110

AN:

152012

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000759

Gnomad4 NFE

AF:

0.000942

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.000691

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ARIH1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

May 16, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over