Variant 1-236686477-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000651187.1(ACTN2):c.-91+9367C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 344,000 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

ACTN2
ENST00000651187.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.78

Variant links:

Genes affected

ACTN2 (HGNC:164): (actinin alpha 2) 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 muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

ACTN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 1-236686477-C-A is Benign according to our data. Variant chr1-236686477-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1186931.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00589 (881/149548) while in subpopulation AFR AF= 0.0205 (844/41174). AF 95% confidence interval is 0.0194. There are 6 homozygotes in gnomad4. There are 397 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 881 AD gene.

Transcripts

RefSeq

Gene	Transcript	Effect	MANE	Protein
ACTN2	NM_001103.4 linkuse as main transcript	upstream_gene_variant	ENST00000366578.6	NP_001094.1
ACTN2	NM_001278343.2 linkuse as main transcript	upstream_gene_variant		NP_001265272.1
ACTN2	NR_184402.1 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ACTN2	ENST00000651187.1 linkuse as main transcript	c.-91+9367C>A	intron_variant			ENSP00000498348
ACTN2	ENST00000366578.6 linkuse as main transcript		upstream_gene_variant	1	NM_001103.4	ENSP00000355537	A1	P35609-1
ACTN2	ENST00000542672.7 linkuse as main transcript		upstream_gene_variant	1		ENSP00000443495	P3	P35609-2
ACTN2	ENST00000652096.1 linkuse as main transcript		upstream_gene_variant			ENSP00000498896

Frequencies

GnomAD3 genomes

AF:

0.00589

AC:

880

AN:

149440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00187

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00390

GnomAD4 exome

AF:

0.000561

AC:

109

AN:

194452

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

AN XY:

97692

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.00151

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000632

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.00589

AC:

881

AN:

149548

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

397

AN XY:

72986

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.00186

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00386

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.1

DANN

Benign

0.93

Splicing

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