rs1043374

Positions:

• chr15-97973392-A-C
• chr15-97973392-A-G

Variant summary

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

The NM_183376.3(ARRDC4):​c.*2205A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,410 control chromosomes in the GnomAD database, including 25,899 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 0.57 (25861 hom., cov: 33)
  • Exomes 𝑓: 0.52 (38 hom.)
• Consequence: ARRDC4 NM_183376.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

Genes affected

ARRDC4 (HGNC:28087): (arrestin domain containing 4) Predicted to enable ubiquitin ligase-substrate adaptor activity. Acts upstream of or within positive regulation of ubiquitin-protein transferase activity. Located in endosome and plasma membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRDC4	NM_183376.3	c.*2205A>C		3_prime_UTR_variant	8/8	ENST00000268042.7	NP_899232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRDC4	ENST00000268042.7	c.*2205A>C		3_prime_UTR_variant	8/8	1	NM_183376.3	ENSP00000268042.6

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87155 AN: 151976 Hom.: 25843 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.519 AC: 163 AN: 314 Hom.: 38 Cov.: 0 AF XY: 0.515 AC XY: 100 AN XY: 194

Gnomad4 FIN exome AF: 0.519

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.573 AC: 87213 AN: 152096 Hom.: 25861 Cov.: 33 AF XY: 0.574 AC XY: 42672 AN XY: 74338

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.587

Alfa AF: 0.620 Hom.: 50655

Bravo AF: 0.571

Asia WGS AF: 0.769 AC: 2676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1043374; hg19: chr15-98516622;