rs79074016

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001101.5(ACTB):c.426G>T(p.Leu142=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,613,986 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 33 hom. )

Consequence

ACTB
NM_001101.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 7.75

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 7-5528657-C-A is Benign according to our data. Variant chr7-5528657-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 381870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5528657-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00356 (543/152322) while in subpopulation NFE AF= 0.00551 (375/68038). AF 95% confidence interval is 0.00505. There are 1 homozygotes in gnomad4. There are 230 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 543 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTB	NM_001101.5 linkuse as main transcript	c.426G>T	p.Leu142=	synonymous_variant	4/6	ENST00000646664.1	NP_001092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTB	ENST00000646664.1 linkuse as main transcript	c.426G>T	p.Leu142=	synonymous_variant	4/6		NM_001101.5	ENSP00000494750	P1

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

542

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00551

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00463

AC:

1163

AN:

251280

Hom.:

AF XY:

0.00465

AC XY:

631

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.00552

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00425

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00548

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.00575

AC:

8398

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00575

AC XY:

4183

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00514

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00438

Gnomad4 FIN exome

AF:

0.00169

Gnomad4 NFE exome

AF:

0.00623

Gnomad4 OTH exome

AF:

0.00589

GnomAD4 genome

AF:

0.00356

AC:

543

AN:

152322

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

230

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00551

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00608

Hom.:

Bravo

AF:

0.00386

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00717

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ACTB: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 22, 2017	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. -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Baraitser-Winter syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

- -

ACTB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Baraitser-Winter syndrome 1;C5848323:Developmental malformations-deafness-dystonia syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 19, 2021

- -

Developmental malformations-deafness-dystonia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.95

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