chr15-72474873-T-TGGC

Variant names:

• chr15-72474873-T-TGGC
• rs375614248
• NM_005744.5:c.255_257dupCGG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005744.5(ARIH1):​c.255_257dupCGG​(p.Gly86dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 1,412,176 control chromosomes in the GnomAD database, including 2,491 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G86G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.057 (340 hom., cov: 32)
  • Exomes 𝑓: 0.070 (2151 hom.)
• Consequence: ARIH1 NM_005744.5 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.74
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 15-72474873-T-TGGC is Benign according to our data. Variant chr15-72474873-T-TGGC is described in ClinVar as Benign. ClinVar VariationId is 402394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

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.255_257dupCGG	p.Gly86dup	disruptive_inframe_insertion	Exon 1 of 14	NP_005735.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.255_257dupCGG	p.Gly86dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000369217.4
	ARIH1	ENST00000915026.1		c.255_257dupCGG	p.Gly86dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.255_257dupCGG	p.Gly86dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8521 AN: 149668 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00337

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.000786

Gnomad SAS AF: 0.0210

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0645

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0650

GnomAD2 exomes AF: 0.0577 AC: 3555 AN: 61656 AF XY: 0.0549

Gnomad AFR exome AF: 0.00701

Gnomad AMR exome AF: 0.0304

Gnomad ASJ exome AF: 0.0662

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0580

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0696 AC: 87828 AN: 1262402 Hom.: 2151 Cov.: 30 AF XY: 0.0681 AC XY: 42151 AN XY: 619134

African (AFR) AF: 0.00980 AC: 257 AN: 26218

American (AMR) AF: 0.0311 AC: 671 AN: 21594

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 1281 AN: 20204

East Asian (EAS) AF: 0.000360 AC: 10 AN: 27798

South Asian (SAS) AF: 0.0186 AC: 1088 AN: 58434

European-Finnish (FIN) AF: 0.111 AC: 4725 AN: 42698

Middle Eastern (MID) AF: 0.0652 AC: 325 AN: 4986

European-Non Finnish (NFE) AF: 0.0757 AC: 76343 AN: 1009012

Other (OTH) AF: 0.0608 AC: 3128 AN: 51458

GnomAD4 genome AF: 0.0569 AC: 8528 AN: 149774 Hom.: 340 Cov.: 32 AF XY: 0.0586 AC XY: 4286 AN XY: 73138

African (AFR) AF: 0.0133 AC: 543 AN: 40764

American (AMR) AF: 0.0544 AC: 821 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 255 AN: 3442

East Asian (EAS) AF: 0.000788 AC: 4 AN: 5076

South Asian (SAS) AF: 0.0223 AC: 104 AN: 4666

European-Finnish (FIN) AF: 0.120 AC: 1218 AN: 10164

Middle Eastern (MID) AF: 0.0724 AC: 21 AN: 290

European-Non Finnish (NFE) AF: 0.0806 AC: 5427 AN: 67324

Other (OTH) AF: 0.0638 AC: 132 AN: 2068

Alfa AF: 0.0271 Hom.: 24

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ARIH1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=82/18	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs375614248; hg19: chr15-72767214; COSMIC: COSV65910958; COSMIC: COSV65910958;