rs852423

Variant names:

Variant summary

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

The NM_001101.5(ACTB):c.364-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,612,274 control chromosomes in the GnomAD database, including 157,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.51 ( 21479 hom., cov: 33)

Exomes 𝑓: 0.43 ( 136509 hom. )

Consequence

ACTB
NM_001101.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.61

Publications

21 publications found

Variant links:

Genes affected

ACTB (HGNC:132): (actin beta) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a major constituent of the contractile apparatus and one of the two nonmuscle cytoskeletal actins that are ubiquitously expressed. Mutations in this gene cause Baraitser-Winter syndrome 1, which is characterized by intellectual disability with a distinctive facial appearance in human patients. Numerous pseudogenes of this gene have been identified throughout the human genome. [provided by RefSeq, Aug 2017]

ACTB Gene-Disease associations (from GenCC):

Baraitser-Winter cerebrofrontofacial syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Baraitser-Winter syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
developmental malformations-deafness-dystonia syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, Genomics England PanelApp
ACTB-associated syndromic thrombocytopenia
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics, ClinGen

ACTB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-5528735-A-G is Benign according to our data. Variant chr7-5528735-A-G is described in ClinVar as Benign. ClinVar VariationId is 379378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTB	NM_001101.5	MANE Select	c.364-16T>C		intron	N/A	NP_001092.1	P60709

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTB	ENST00000646664.1	MANE Select	c.364-16T>C	intron	N/A	ENSP00000494750.1	P60709
ACTB	ENST00000425660.5	TSL:1	n.*27-16T>C	intron	N/A	ENSP00000409264.1	G5E9R0
ACTB	ENST00000493945.6	TSL:5	c.364-16T>C	intron	N/A	ENSP00000494269.1	P60709

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77230

AN:

151942

Hom.:

21433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.497

GnomAD2 exomes

AF:

0.435

AC:

108520

AN:

249490

AF XY:

0.431

show subpopulations

Gnomad AFR exome

AF:

0.755

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.532

Gnomad EAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.427

AC:

623418

AN:

1460214

Hom.:

136509

Cov.:

AF XY:

0.426

AC XY:

309661

AN XY:

726516

show subpopulations

African (AFR)

AF:

0.764

AC:

25573

AN:

33474

American (AMR)

AF:

0.400

AC:

17905

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

13890

AN:

26134

East Asian (EAS)

AF:

0.278

AC:

11016

AN:

39688

South Asian (SAS)

AF:

0.406

AC:

35040

AN:

86238

European-Finnish (FIN)

AF:

0.444

AC:

23373

AN:

52636

Middle Eastern (MID)

AF:

0.503

AC:

2899

AN:

5766

European-Non Finnish (NFE)

AF:

0.421

AC:

467319

AN:

1111208

Other (OTH)

AF:

0.437

AC:

26403

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

20089

40178

60266

80355

100444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14434

28868

43302

57736

72170

<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:

0.509

AC:

77334

AN:

152060

Hom.:

21479

Cov.:

AF XY:

0.506

AC XY:

37575

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.751

AC:

31151

AN:

41490

American (AMR)

AF:

0.421

AC:

6422

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1890

AN:

3472

East Asian (EAS)

AF:

0.293

AC:

1511

AN:

5162

South Asian (SAS)

AF:

0.391

AC:

1884

AN:

4816

European-Finnish (FIN)

AF:

0.435

AC:

4600

AN:

10576

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.417

AC:

28363

AN:

67962

Other (OTH)

AF:

0.497

AC:

1051

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1813

3626

5440

7253

9066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.433

Hom.:

17039

Bravo

AF:

0.519

Asia WGS

AF:

0.391

AC:

1359

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Baraitser-Winter syndrome 1 (2)

Developmental malformations-deafness-dystonia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.49

(source)

DANN

Benign

0.33

PhyloP100

-1.6

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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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