chr15-97972903-C-T

Position:

• chr15-97972903-C-T

Variant summary

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

The NM_183376.3(ARRDC4):​c.*1716C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,504 control chromosomes in the GnomAD database, including 24,536 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 0.55 (24480 hom., cov: 33)
  • Exomes 𝑓: 0.52 (56 hom.)
• Consequence: ARRDC4 NM_183376.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRDC4	NM_183376.3	c.*1716C>T		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.*1716C>T		3_prime_UTR_variant	8/8	1	NM_183376.3	ENSP00000268042.6

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83946 AN: 151954 Hom.: 24473 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.516 AC: 223 AN: 432 Hom.: 56 Cov.: 0 AF XY: 0.516 AC XY: 133 AN XY: 258

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.552 AC: 83977 AN: 152072 Hom.: 24480 Cov.: 33 AF XY: 0.554 AC XY: 41158 AN XY: 74352

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.570

Alfa AF: 0.596 Hom.: 11916

Bravo AF: 0.546

Asia WGS AF: 0.759 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.49

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: rs1043372; hg19: chr15-98516133; COSMIC: COSV51419592;