8-142612050-C-T

Position:

• chr8-142612050-C-T

Variant summary

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

The NM_001412852.1(ARC):​c.*800G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,740 control chromosomes in the GnomAD database, including 6,030 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 0.27 (6010 hom., cov: 33)
  • Exomes 𝑓: 0.22 (20 hom.)
• Consequence: ARC NM_001412852.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

Genes affected

ARC (HGNC:648): (activity regulated cytoskeleton associated protein) Predicted to enable mRNA binding activity. Involved in cell migration; cytoskeleton organization; and regulation of cell morphogenesis. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARC	NM_015193.5	c.*742+58G>A		intron_variant		ENST00000356613.4	NP_056008.1
ARC	NM_001412852.1	c.*800G>A		3_prime_UTR_variant	2/2		NP_001399781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARC	ENST00000356613.4	c.*742+58G>A		intron_variant		1	NM_015193.5	ENSP00000349022.2
ARC	ENST00000581404.1	n.*15G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41512 AN: 151858 Hom.: 6012 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.220 AC: 168 AN: 764 Hom.: 20 Cov.: 0 AF XY: 0.209 AC XY: 106 AN XY: 508

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.273 AC: 41548 AN: 151976 Hom.: 6010 Cov.: 33 AF XY: 0.273 AC XY: 20291 AN XY: 74256

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.274

Alfa AF: 0.147 Hom.: 307

Bravo AF: 0.276

Asia WGS AF: 0.233 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.82

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: rs35900184; hg19: chr8-143693411;