15-72474756-C-T

Variant names:

• chr15-72474756-C-T
• rs781108925
• NM_005744.5:c.117C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_005744.5(ARIH1):​c.117C>T​(p.Thr39Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARIH1 NM_005744.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.50
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 15-72474756-C-T is Benign according to our data. Variant chr15-72474756-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2994735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.5 with no splicing effect.

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.117C>T	p.Thr39Thr	synonymous	Exon 1 of 14	NP_005735.2	Q9Y4X5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.117C>T	p.Thr39Thr	synonymous	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
	ARIH1	ENST00000915026.1		c.117C>T	p.Thr39Thr	synonymous	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.117C>T	p.Thr39Thr	synonymous	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000491 AC: 1 AN: 203662 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1401020 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 697238

African (AFR) AF: 0.00 AC: 0 AN: 29024

American (AMR) AF: 0.00 AC: 0 AN: 37496

Ashkenazi Jewish (ASJ) AF: 0.0000413 AC: 1 AN: 24212

East Asian (EAS) AF: 0.00 AC: 0 AN: 32844

South Asian (SAS) AF: 0.00 AC: 0 AN: 79660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5570

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082436

Other (OTH) AF: 0.00 AC: 0 AN: 57450

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Uncertain	0.97
PhyloP100		2.5
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

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: rs781108925; hg19: chr15-72767097;