Variant 1-229432520-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001100.4(ACTA1):c.454+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,371,116 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

ACTA1
NM_001100.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

ACTA1 (HGNC:129): (actin alpha 1, skeletal muscle) The product encoded by this gene belongs to the actin family of proteins, which are highly conserved proteins that play a role in cell motility, structure and integrity. Alpha, beta and gamma actin isoforms have been identified, with alpha actins being a major constituent of the contractile apparatus, while beta and gamma actins are involved in the regulation of cell motility. This actin is an alpha actin that is found in skeletal muscle. Mutations in this gene cause a variety of myopathies, including nemaline myopathy, congenital myopathy with excess of thin myofilaments, congenital myopathy with cores, and congenital myopathy with fiber-type disproportion, diseases that lead to muscle fiber defects with manifestations such as hypotonia. [provided by RefSeq, Sep 2019]

ACTA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-229432520-G-A is Benign according to our data. Variant chr1-229432520-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000819 (120/146500) while in subpopulation NFE AF= 0.00131 (86/65648). AF 95% confidence interval is 0.00109. There are 0 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTA1	NM_001100.4 linkuse as main transcript	c.454+36C>T		intron_variant		ENST00000366684.7	NP_001091.1	P68133

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ACTA1	ENST00000366684.7 linkuse as main transcript	c.454+36C>T	intron_variant	1	NM_001100.4	ENSP00000355645.3	P68133
ACTA1	ENST00000366683.4 linkuse as main transcript	c.454+36C>T	intron_variant	5		ENSP00000355644.4	A6NL76
ACTA1	ENST00000684723.1 linkuse as main transcript	c.319+36C>T	intron_variant			ENSP00000508084.1	A0A804HKV3

Frequencies

GnomAD3 genomes

AF:

0.000820

AC:

120

AN:

146410

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000518

Gnomad AMI

AF:

0.00229

Gnomad AMR

AF:

0.0000670

Gnomad ASJ

AF:

0.000299

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000885

Gnomad FIN

AF:

0.000105

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00148

GnomAD3 exomes

AF:

0.00103

AC:

155

AN:

150756

Hom.:

AF XY:

0.00117

AC XY:

AN XY:

80082

show subpopulations

Gnomad AFR exome

AF:

0.000341

Gnomad AMR exome

AF:

0.000982

Gnomad ASJ exome

AF:

0.000341

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00194

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00132

AC:

1614

AN:

1224616

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

827

AN XY:

606168

show subpopulations

Gnomad4 AFR exome

AF:

0.000173

Gnomad4 AMR exome

AF:

0.000717

Gnomad4 ASJ exome

AF:

0.0000945

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00162

Gnomad4 FIN exome

AF:

0.0000230

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00120

GnomAD4 genome

AF:

0.000819

AC:

120

AN:

146500

Hom.:

Cov.:

AF XY:

0.000702

AC XY:

AN XY:

71264

show subpopulations

Gnomad4 AFR

AF:

0.000517

Gnomad4 AMR

AF:

0.0000670

Gnomad4 ASJ

AF:

0.000299

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000885

Gnomad4 FIN

AF:

0.000105

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00146

Alfa

AF:

0.000819

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.5

DANN

Benign

0.81

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