rs2273419

Positions:

• chr14-68884044-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001130004.2(ACTN1):​c.1635+124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,046,124 control chromosomes in the GnomAD database, including 6,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1135 hom., cov: 32)
  • Exomes 𝑓: 0.10 (5199 hom.)
• Consequence: ACTN1 NM_001130004.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-68884044-G-T is Benign according to our data. Variant chr14-68884044-G-T is described in ClinVar as [Benign]. Clinvar id is 1225619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN1	NM_001130004.2	c.1635+124C>A		intron_variant		ENST00000394419.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN1	ENST00000394419.9	c.1635+124C>A		intron_variant		1	NM_001130004.2	P3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17794 AN: 152028 Hom.: 1129 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.104 AC: 93367 AN: 893978 Hom.: 5199 AF XY: 0.105 AC XY: 46279 AN XY: 441772

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0663

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.0719

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.117 AC: 17825 AN: 152146 Hom.: 1135 Cov.: 32 AF XY: 0.118 AC XY: 8790 AN XY: 74398

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0756

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0535

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.116

Alfa AF: 0.103 Hom.: 1247

Bravo AF: 0.113

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.63

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: rs2273419; hg19: chr14-69350761;