rs10518993

chr15-72568723-C-Achr15-72568723-C-Gchr15-72568723-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005744.5(ARIH1):c.1027-1454C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,140 control chromosomes in the GnomAD database, including 60,960 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (60960 hom., cov: 32)
• Consequence: ARIH1 NM_005744.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARIH1	NM_005744.5	c.1027-1454C>A		intron_variant		ENST00000379887.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARIH1	ENST00000379887.9	c.1027-1454C>A		intron_variant		1	NM_005744.5	P1
ARIH1	ENST00000561987.5	n.98+7174C>A		intron_variant, non_coding_transcript_variant		3
ARIH1	ENST00000565950.1	n.309-1441C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133088 AN: 152022 Hom.: 60945 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.906

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.875 AC: 133148 AN: 152140 Hom.: 60960 Cov.: 32 AF XY: 0.880 AC XY: 65488 AN XY: 74378

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.907

Alfa AF: 0.916 Hom.: 3433

Bravo AF: 0.857

Asia WGS AF: 0.975 AC: 3386 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.62
Dann	Benign	0.35

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: rs10518993; hg19: chr15-72861064;