Variant 14-68925547-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001130004.2(ACTN1):c.220+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,606,296 control chromosomes in the GnomAD database, including 342,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.69 ( 36598 hom., cov: 29)

Exomes 𝑓: 0.64 ( 306198 hom. )

Consequence

ACTN1
NM_001130004.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.136

Variant links:

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]

ACTN1 links:

ACTN1 (HGNC:):

ACTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 14-68925547-T-G is Benign according to our data. Variant chr14-68925547-T-G is described in ClinVar as [Benign]. Clinvar id is 2414021.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTN1	NM_001130004.2 linkuse as main transcript	c.220+11A>C		intron_variant		ENST00000394419.9	NP_001123476.1	P12814-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN1	ENST00000394419.9 linkuse as main transcript	c.220+11A>C		intron_variant		1	NM_001130004.2	ENSP00000377941.4		P12814-3

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104240

AN:

151748

Hom.:

36548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.566

Gnomad EAS

AF:

0.990

Gnomad SAS

AF:

0.879

Gnomad FIN

AF:

0.709

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.663

GnomAD3 exomes

AF:

0.713

AC:

175806

AN:

246644

Hom.:

64795

AF XY:

0.710

AC XY:

94655

AN XY:

133228

show subpopulations

Gnomad AFR exome

AF:

0.756

Gnomad AMR exome

AF:

0.823

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.990

Gnomad SAS exome

AF:

0.863

Gnomad FIN exome

AF:

0.709

Gnomad NFE exome

AF:

0.604

Gnomad OTH exome

AF:

0.671

GnomAD4 exome

AF:

0.641

AC:

932609

AN:

1454430

Hom.:

306198

Cov.:

AF XY:

0.647

AC XY:

467934

AN XY:

723460

show subpopulations

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.810

Gnomad4 ASJ exome

AF:

0.563

Gnomad4 EAS exome

AF:

0.990

Gnomad4 SAS exome

AF:

0.861

Gnomad4 FIN exome

AF:

0.704

Gnomad4 NFE exome

AF:

0.600

Gnomad4 OTH exome

AF:

0.655

GnomAD4 genome

AF:

0.687

AC:

104352

AN:

151866

Hom.:

36598

Cov.:

AF XY:

0.700

AC XY:

51918

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.755

Gnomad4 AMR

AF:

0.729

Gnomad4 ASJ

AF:

0.566

Gnomad4 EAS

AF:

0.990

Gnomad4 SAS

AF:

0.879

Gnomad4 FIN

AF:

0.709

Gnomad4 NFE

AF:

0.604

Gnomad4 OTH

AF:

0.666

Alfa

AF:

0.625

Hom.:

59774

Bravo

AF:

0.688

Asia WGS

AF:

0.914

AC:

3177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.8

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over