rs13447394

Positions:

chr7-5529667-C-A

Variant summary

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

The NM_001101.5(ACTB):c.-6-4G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,610,772 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 23 hom. )

Consequence

ACTB
NM_001101.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008179

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.101

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

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 7-5529667-C-A is Benign according to our data. Variant chr7-5529667-C-A is described in ClinVar as [Benign]. Clinvar id is 195111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5529667-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00318 (484/152302) while in subpopulation NFE AF= 0.00568 (386/67992). AF 95% confidence interval is 0.00521. There are 1 homozygotes in gnomad4. There are 213 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 484 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTB	NM_001101.5 linkuse as main transcript	c.-6-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.-6-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001101.5	ENSP00000494750	P1

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

484

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00771

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00568

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00303

AC:

737

AN:

243158

Hom.:

AF XY:

0.00302

AC XY:

403

AN XY:

133468

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.000843

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00270

Gnomad NFE exome

AF:

0.00531

Gnomad OTH exome

AF:

0.00318

GnomAD4 exome

AF:

0.00479

AC:

6985

AN:

1458470

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

3382

AN XY:

725636

show subpopulations

Gnomad4 AFR exome

AF:

0.000718

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.00289

Gnomad4 NFE exome

AF:

0.00581

Gnomad4 OTH exome

AF:

0.00327

GnomAD4 genome

AF:

0.00318

AC:

484

AN:

152302

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00568

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00447

Hom.:

Bravo

AF:

0.00319

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00468

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 02, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 22, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	ACTB: BS1, BS2 -

Baraitser-Winter syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 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

-0.77

CADD

Benign

6.6

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.060

SpliceAI score (max)

0.010

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