rs723113

Positions:

• chr14-68919038-C-T

Variant summary

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

The ENST00000394419.9(ACTN1):​c.340+1968G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,126 control chromosomes in the GnomAD database, including 20,931 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 0.52 (20931 hom., cov: 33)
• Consequence: ACTN1 ENST00000394419.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTN1	NM_001130004.2	c.340+1968G>A		intron_variant		ENST00000394419.9	NP_001123476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN1	ENST00000394419.9	c.340+1968G>A		intron_variant		1	NM_001130004.2	ENSP00000377941	P3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78796 AN: 152008 Hom.: 20897 Cov.: 33

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.519 AC: 78879 AN: 152126 Hom.: 20931 Cov.: 33 AF XY: 0.520 AC XY: 38655 AN XY: 74338

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.486

Alfa AF: 0.484 Hom.: 24994

Bravo AF: 0.519

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.68

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: rs723113; hg19: chr14-69385755;