rs1374092

Positions:

• chr15-72516087-G-T

Variant summary

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

The NM_005744.5(ARIH1):​c.376-1980G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,122 control chromosomes in the GnomAD database, including 47,041 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 0.73 (47041 hom., cov: 31)
• Consequence: ARIH1 NM_005744.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.376-1980G>T		intron_variant		ENST00000379887.9	NP_005735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARIH1	ENST00000379887.9	c.376-1980G>T		intron_variant		1	NM_005744.5	ENSP00000369217	P1
ARIH1	ENST00000564062.1	c.371-1980G>T		intron_variant		3		ENSP00000454774
ARIH1	ENST00000570085.5	c.376-1980G>T		intron_variant, NMD_transcript_variant		3		ENSP00000456746
ARIH1	ENST00000567762.1	n.148-1980G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111247 AN: 152004 Hom.: 47056 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.731 AC: 111240 AN: 152122 Hom.: 47041 Cov.: 31 AF XY: 0.737 AC XY: 54819 AN XY: 74386

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.773

Alfa AF: 0.895 Hom.: 106900

Bravo AF: 0.700

Asia WGS AF: 0.825 AC: 2868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.42

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: rs1374092; hg19: chr15-72808428;