Variant chr7-100643148-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016188.5(ACTL6B):c.*98T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,240,224 control chromosomes in the GnomAD database, including 447,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59308 hom., cov: 30)

Exomes 𝑓: 0.84 ( 388040 hom. )

Consequence

ACTL6B
NM_016188.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0180

Variant links:

Genes affected

ACTL6B (HGNC:160): (actin like 6B) The protein encoded by this gene is a member of a family of actin-related proteins (ARPs) which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene encodes a subunit of the BAF (BRG1/brm-associated factor) complex in mammals, which is functionally related to SWI/SNF complex in S. cerevisiae and Drosophila; the latter is thought to facilitate transcriptional activation of specific genes by antagonizing chromatin-mediated transcriptional repression. This subunit may be involved in the regulation of genes by structural modulation of their chromatin, specifically in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACTL6B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-100643148-A-T is Benign according to our data. Variant chr7-100643148-A-T is described in ClinVar as [Benign]. Clinvar id is 1188858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTL6B	NM_016188.5 link	c.*98T>A		3_prime_UTR_variant	14/14	ENST00000160382.10	NP_057272.1	O94805
ACTL6B	NR_134539.2 link	n.1490T>A		non_coding_transcript_exon_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTL6B	ENST00000160382 link	c.*98T>A		3_prime_UTR_variant	14/14	1	NM_016188.5	ENSP00000160382.5		O94805
ACTL6B	ENST00000487125.1 link	n.941T>A		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.881

AC:

133836

AN:

151968

Hom.:

59250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.969

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.904

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.761

Gnomad FIN

AF:

0.824

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.839

Gnomad OTH

AF:

0.875

GnomAD4 exome

AF:

0.843

AC:

917506

AN:

1088138

Hom.:

388040

Cov.:

AF XY:

0.839

AC XY:

461575

AN XY:

550184

show subpopulations

Gnomad4 AFR exome

AF:

0.975

Gnomad4 AMR exome

AF:

0.899

Gnomad4 ASJ exome

AF:

0.878

Gnomad4 EAS exome

AF:

0.933

Gnomad4 SAS exome

AF:

0.760

Gnomad4 FIN exome

AF:

0.830

Gnomad4 NFE exome

AF:

0.839

Gnomad4 OTH exome

AF:

0.856

GnomAD4 genome

AF:

0.881

AC:

133953

AN:

152086

Hom.:

59308

Cov.:

AF XY:

0.879

AC XY:

65375

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.969

Gnomad4 AMR

AF:

0.904

Gnomad4 ASJ

AF:

0.882

Gnomad4 EAS

AF:

0.906

Gnomad4 SAS

AF:

0.760

Gnomad4 FIN

AF:

0.824

Gnomad4 NFE

AF:

0.839

Gnomad4 OTH

AF:

0.875

Alfa

AF:

0.812

Hom.:

2874

Bravo

AF:

0.893

Asia WGS

AF:

0.834

AC:

2903

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual developmental disorder with severe speech and ambulation defects

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Developmental and epileptic encephalopathy, 76

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.5

DANN

Benign

0.65

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