rs1374092

Variant names:

• chr15-72516087-G-T
• rs1374092
• NM_005744.5:c.376-1980G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.376-1980G>T		intron_variant	Intron 1 of 13	ENST00000379887.9	NP_005735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARIH1	ENST00000379887.9	c.376-1980G>T		intron_variant	Intron 1 of 13	1	NM_005744.5	ENSP00000369217.4
ARIH1	ENST00000564062.1	c.370-1980G>T		intron_variant	Intron 1 of 3	3		ENSP00000454774.1
ARIH1	ENST00000567762.1	n.148-1980G>T		intron_variant	Intron 2 of 3	3
ARIH1	ENST00000570085.5	n.376-1980G>T		intron_variant	Intron 1 of 4	3		ENSP00000456746.1

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

African (AFR) AF: 0.268 AC: 11120 AN: 41442

American (AMR) AF: 0.815 AC: 12454 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3180 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4308 AN: 5172

South Asian (SAS) AF: 0.903 AC: 4359 AN: 4826

European-Finnish (FIN) AF: 0.953 AC: 10109 AN: 10610

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62947 AN: 68010

Other (OTH) AF: 0.773 AC: 1632 AN: 2112

Alfa AF: 0.864 Hom.: 136051

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
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1374092; hg19: chr15-72808428;