rs2268983

chr14-68941980-G-Achr14-68941980-G-Cchr14-68941980-G-T

Variant summary

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

The NM_001130004.2(ACTN1):c.106-16308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,990 control chromosomes in the GnomAD database, including 31,236 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 0.63 (31236 hom., cov: 31)
• Consequence: ACTN1 NM_001130004.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN1	NM_001130004.2	c.106-16308C>T		intron_variant		ENST00000394419.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN1	ENST00000394419.9	c.106-16308C>T		intron_variant		1	NM_001130004.2	P3

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95254 AN: 151872 Hom.: 31181 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.628 AC: 95381 AN: 151990 Hom.: 31236 Cov.: 31 AF XY: 0.636 AC XY: 47197 AN XY: 74262

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.576

Alfa AF: 0.531 Hom.: 49724

Bravo AF: 0.624

Asia WGS AF: 0.738 AC: 2569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.9
Dann	Benign	0.51

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: rs2268983; hg19: chr14-69408697;