NM_183376.3:c.*2205A>C

Variant names:

• chr15-97973392-A-C
• rs1043374
• NM_183376.3:c.*2205A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ENSG00000259199 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARRDC4	NM_183376.3	c.*2205A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000268042.7	NP_899232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRDC4	ENST00000268042.7	c.*2205A>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_183376.3	ENSP00000268042.6
ENSG00000259199	ENST00000717124.1	n.364+73275T>G		intron_variant	Intron 4 of 8

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.519 AC: 161 AN: 310

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.433 AC: 17972 AN: 41492

American (AMR) AF: 0.589 AC: 8985 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2297 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4584 AN: 5174

South Asian (SAS) AF: 0.749 AC: 3611 AN: 4818

European-Finnish (FIN) AF: 0.508 AC: 5372 AN: 10574

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42423 AN: 67984

Other (OTH) AF: 0.587 AC: 1238 AN: 2110

Alfa AF: 0.608 Hom.: 80894

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
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1043374; hg19: chr15-98516622;