2-113957956-G-A

Position:

• chr2-113957956-G-A

Variant summary

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

The ENST00000263238.7(ACTR3):​c.*501G>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 0.466 in 152,620 control chromosomes in the GnomAD database, including 20,296 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 0.47 (20170 hom., cov: 31)
  • Exomes 𝑓: 0.60 (126 hom.)
• Consequence: ACTR3 ENST00000263238.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

Genes affected

ACTR3 (HGNC:170): (actin related protein 3) The specific function of this gene has not yet been determined; however, the protein it encodes is known to be a major constituent of the ARP2/3 complex. This complex is located at the cell surface and is essential to cell shape and motility through lamellipodial actin assembly and protrusion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR3	NM_005721.5	c.*501G>A		3_prime_UTR_variant	12/12	ENST00000263238.7	NP_005712.1
ACTR3	NM_001277140.1	c.*501G>A		3_prime_UTR_variant	12/12		NP_001264069.1
ACTR3	NR_102318.1	n.1979G>A		non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR3	ENST00000263238.7	c.*501G>A		3_prime_UTR_variant	12/12	1	NM_005721.5	ENSP00000263238	P1
ACTR3	ENST00000478928.1	n.5332G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70699 AN: 151828 Hom.: 20177 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.596 AC: 402 AN: 674 Hom.: 126 Cov.: 0 AF XY: 0.607 AC XY: 215 AN XY: 354

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.465 AC: 70684 AN: 151946 Hom.: 20170 Cov.: 31 AF XY: 0.469 AC XY: 34842 AN XY: 74240

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.509

Alfa AF: 0.497 Hom.: 4092

Bravo AF: 0.432

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.60
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: rs6642; hg19: chr2-114715533;