rs852423

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 379378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5528735-A-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTB	NM_001101.5 link	c.364-16T>C		intron_variant	Intron 3 of 5	ENST00000646664.1	NP_001092.1	P60709Q1KLZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTB	ENST00000646664.1 link	c.364-16T>C		intron_variant	Intron 3 of 5		NM_001101.5	ENSP00000494750.1		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

GnomAD3 exomes

AF:

0.435

AC:

108520

AN:

249490

Hom.:

24897

AF XY:

0.431

AC XY:

58430

AN XY:

135430

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 SAS exome

AF:

0.407

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

Gnomad4 AFR exome

AF:

0.764

Gnomad4 AMR exome

AF:

0.400

Gnomad4 ASJ exome

AF:

0.531

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.509

AC:

77334

AN:

152060

Hom.:

21479

Cov.:

AF XY:

0.506

AC XY:

37575

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.751

Gnomad4 AMR

AF:

0.421

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.391

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.417

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.422

Hom.:

8366

Bravo

AF:

0.519

Asia WGS

AF:

0.391

AC:

1359

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 23, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Baraitser-Winter syndrome 1

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental malformations-deafness-dystonia syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.49

DANN

Benign

0.33

BranchPoint Hunter

1.0

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