rs1475034

Variant names:

• chr14-68874043-G-T
• rs1475034
• NM_001130004.2:c.*816C>A

Variant summary

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

The NM_001130004.2(ACTN1):​c.*816C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,110 control chromosomes in the GnomAD database, including 4,484 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 0.24 (4482 hom., cov: 32)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: ACTN1 NM_001130004.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630

Genes affected

ACTN1 (HGNC:163): (actinin alpha 1) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, cytoskeletal, alpha actinin isoform and maps to the same site as the structurally similar erythroid beta spectrin gene. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN1	NM_001130004.2	c.*816C>A		downstream_gene_variant		ENST00000394419.9	NP_001123476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTN1	ENST00000394419.9	c.*816C>A		downstream_gene_variant		1	NM_001130004.2	ENSP00000377941.4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36193 AN: 151838 Hom.: 4479 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.234 AC: 36 AN: 154 Hom.: 2 AF XY: 0.239 AC XY: 21 AN XY: 88

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.400

GnomAD4 genome AF: 0.238 AC: 36216 AN: 151956 Hom.: 4482 Cov.: 32 AF XY: 0.235 AC XY: 17469 AN XY: 74278

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0648

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.231

Alfa AF: 0.245 Hom.: 6771

Bravo AF: 0.229

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1475034; hg19: chr14-69340760;