15-72474693-TGAG-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005744.5(ARIH1):c.60_62del(p.Glu20del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000444 in 1,570,930 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (11 hom.)
• Consequence: ARIH1 NM_005744.5 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.01

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 15-72474693-TGAG-T is Benign according to our data. Variant chr15-72474693-TGAG-T is described in ClinVar as [Benign]. Clinvar id is 1658666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARIH1	NM_005744.5	c.60_62del	p.Glu20del	inframe_deletion	1/14	ENST00000379887.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARIH1	ENST00000379887.9	c.60_62del	p.Glu20del	inframe_deletion	1/14	1	NM_005744.5	P1
ARIH1	ENST00000564062.1	c.55_57del	p.Glu19del	inframe_deletion	1/4	3
TMEM202-AS1	ENST00000565181.1	n.473_475del		non_coding_transcript_exon_variant	1/1
ARIH1	ENST00000570085.5	c.60_62del	p.Glu20del	inframe_deletion, NMD_transcript_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 33 AN: 151362 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00562

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.000962

GnomAD3 exomes AF: 0.000929 AC: 191 AN: 205606 Hom.: 3 AF XY: 0.00127 AC XY: 143 AN XY: 112972

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00689

Gnomad FIN exome AF: 0.0000503

Gnomad NFE exome AF: 0.0000428

Gnomad OTH exome AF: 0.000205

GnomAD4 exome AF: 0.000468 AC: 665 AN: 1419460 Hom.: 11 AF XY: 0.000656 AC XY: 463 AN XY: 705880

Gnomad4 AFR exome AF: 0.0000334

Gnomad4 AMR exome AF: 0.000126

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000576

Gnomad4 SAS exome AF: 0.00714

Gnomad4 FIN exome AF: 0.0000192

Gnomad4 NFE exome AF: 0.0000412

Gnomad4 OTH exome AF: 0.000428

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151470 Hom.: 1 Cov.: 32 AF XY: 0.000284 AC XY: 21 AN XY: 74030

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00563

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000907

Asia WGS AF: 0.00234 AC: 8 AN: 3436

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 28, 2023

- -

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: rs534030629; hg19: chr15-72767034;