rs9910792

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001614.5(ACTG1):c.363+13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,613,646 control chromosomes in the GnomAD database, including 171,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15748 hom., cov: 33)

Exomes 𝑓: 0.45 ( 155388 hom. )

Consequence

ACTG1
NM_001614.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.936

Publications

26 publications found

Variant links:

Genes affected

ACTG1 (HGNC:144): (actin gamma 1) Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACTG1 Gene-Disease associations (from GenCC):

Baraitser-winter syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss 20
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Baraitser-Winter cerebrofrontofacial syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACTG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

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

BP6

Variant 17-81511890-G-T is Benign according to our data. Variant chr17-81511890-G-T is described in ClinVar as Benign. ClinVar VariationId is 44147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001614.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTG1	NM_001614.5	MANE Select	c.363+13C>A	intron	N/A	NP_001605.1	P63261
ACTG1	NM_001199954.3		c.363+13C>A	intron	N/A	NP_001186883.1	P63261
ACTG1	NR_037688.3		n.435+13C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTG1	ENST00000573283.7	TSL:5 MANE Select	c.363+13C>A	intron	N/A	ENSP00000458435.1	P63261
ACTG1	ENST00000575842.5	TSL:1	c.363+13C>A	intron	N/A	ENSP00000458162.1	P63261
ACTG1	ENST00000615544.5	TSL:1	c.363+13C>A	intron	N/A	ENSP00000477968.1	P63261

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68121

AN:

151982

Hom.:

15728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.455

GnomAD2 exomes

AF:

0.498

AC:

124455

AN:

250080

AF XY:

0.501

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.505

Gnomad ASJ exome

AF:

0.469

Gnomad EAS exome

AF:

0.875

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.435

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.453

AC:

662233

AN:

1461546

Hom.:

155388

Cov.:

AF XY:

0.459

AC XY:

333405

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.400

AC:

13374

AN:

33470

American (AMR)

AF:

0.504

AC:

22520

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

12227

AN:

26132

East Asian (EAS)

AF:

0.820

AC:

32559

AN:

39696

South Asian (SAS)

AF:

0.611

AC:

52715

AN:

86254

European-Finnish (FIN)

AF:

0.423

AC:

22552

AN:

53328

Middle Eastern (MID)

AF:

0.520

AC:

2992

AN:

5750

European-Non Finnish (NFE)

AF:

0.427

AC:

475157

AN:

1111830

Other (OTH)

AF:

0.466

AC:

28137

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

22427

44854

67282

89709

112136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14684

29368

44052

58736

73420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.448

AC:

68176

AN:

152100

Hom.:

15748

Cov.:

AF XY:

0.454

AC XY:

33724

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.399

AC:

16558

AN:

41478

American (AMR)

AF:

0.471

AC:

7199

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

1630

AN:

3470

East Asian (EAS)

AF:

0.852

AC:

4401

AN:

5164

South Asian (SAS)

AF:

0.629

AC:

3031

AN:

4822

European-Finnish (FIN)

AF:

0.419

AC:

4440

AN:

10590

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.429

AC:

29197

AN:

67984

Other (OTH)

AF:

0.462

AC:

974

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1963

3926

5890

7853

9816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.440

Hom.:

32572

Bravo

AF:

0.452

Asia WGS

AF:

0.695

AC:

2417

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Autosomal dominant nonsyndromic hearing loss 20 (1)

Autosomal dominant nonsyndromic hearing loss 20;C3281235:Baraitser-winter syndrome 2 (1)

Baraitser-winter syndrome 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.013

(source)

DANN

Benign

0.64

PhyloP100

-0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over