Genetic Variant NM_005744.5:c.252_257delCGGCGG (chr15-72474873-TGGCGGC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005744.5(ARIH1):c.252_257delCGGCGG(p.Gly85_Gly86del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,412,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ARIH1
NM_005744.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 14 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.252_257delCGGCGG	p.Gly85_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	NP_005735.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.252_257delCGGCGG	p.Gly85_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000369217.4
ARIH1	ENST00000915026.1		c.252_257delCGGCGG	p.Gly85_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585085.1
ARIH1	ENST00000915024.1		c.252_257delCGGCGG	p.Gly85_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes

AF:

0.0000935

AC:

AN:

149696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000738

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000649

AC:

AN:

61656

AF XY:

0.0000290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000242

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000950

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000107

AC:

135

AN:

1263216

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

619536

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26222

American (AMR)

AF:

0.000139

AC:

AN:

21624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20236

East Asian (EAS)

AF:

0.00

AC:

AN:

27798

South Asian (SAS)

AF:

0.000188

AC:

AN:

58468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42780

Middle Eastern (MID)

AF:

0.00201

AC:

AN:

4984

European-Non Finnish (NFE)

AF:

0.000103

AC:

104

AN:

1009594

Other (OTH)

AF:

0.000116

AC:

AN:

51510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000935

AC:

AN:

149696

Hom.:

Cov.:

AF XY:

0.0000958

AC XY:

AN XY:

73034

show subpopulations

African (AFR)

AF:

0.0000738

AC:

AN:

40650

American (AMR)

AF:

0.0000663

AC:

AN:

15074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000148

AC:

AN:

67346

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000642

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=166/34

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over