NM_005744.5:c.84_86delGGA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 1556148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 110 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.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	Exon 1 of 14	NP_005735.2	Q9Y4X5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
	ARIH1	ENST00000915026.1		c.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.84_86delGGA	p.Glu28del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585083.1

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

GnomAD2 exomes AF: 0.00254 AC: 477 AN: 187818 AF XY: 0.00261

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00905

Gnomad EAS exome AF: 0.00330

Gnomad FIN exome AF: 0.00230

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00276

GnomAD4 exome AF: 0.00130 AC: 1831 AN: 1406978 Hom.: 1 AF XY: 0.00128 AC XY: 898 AN XY: 699658

African (AFR) AF: 0.000884 AC: 26 AN: 29424

American (AMR) AF: 0.00155 AC: 60 AN: 38588

Ashkenazi Jewish (ASJ) AF: 0.00794 AC: 194 AN: 24440

East Asian (EAS) AF: 0.00101 AC: 34 AN: 33710

South Asian (SAS) AF: 0.00122 AC: 97 AN: 79666

European-Finnish (FIN) AF: 0.00171 AC: 89 AN: 51994

Middle Eastern (MID) AF: 0.000537 AC: 3 AN: 5588

European-Non Finnish (NFE) AF: 0.00114 AC: 1241 AN: 1085786

Other (OTH) AF: 0.00151 AC: 87 AN: 57782

GnomAD4 genome AF: 0.000724 AC: 110 AN: 152012 Hom.: 0 Cov.: 32 AF XY: 0.000646 AC XY: 48 AN XY: 74320

African (AFR) AF: 0.000241 AC: 10 AN: 41518

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000759 AC: 8 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000942 AC: 64 AN: 67920

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00409 Hom.: 1

Bravo AF: 0.000691

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ARIH1-related disorder (1)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs143905502; hg19: chr15-72767052; COSMIC: COSV65911671; COSMIC: COSV65911671;