15-72474711-CGAGGAG-CGAG

Variant names:

• chr15-72474711-CGAG-C
• rs143905502
• NM_005744.5:c.84_86delGGA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.77

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]

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

ACMG classification

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 rank	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	Exon 1 of 14	ENST00000379887.9	NP_005735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARIH1	ENST00000379887.9	c.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	Exon 1 of 14	1	NM_005744.5	ENSP00000369217.4

Frequencies

GnomAD3 genomes AF: 0.000724 AC: 110 AN: 151908 Hom.: 0 Cov.: 32

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.: 1 AF XY: 0.00128 AC XY: 898 AN XY: 699658

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.: 0 Cov.: 32 AF XY: 0.000646 AC XY: 48 AN XY: 74320

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

Submissions by phenotype

ARIH1-related disorder Benign:1

Dec 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

May 16, 2023

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs143905502; hg19: chr15-72767052;