Genetic Variant ACTB:c.*95_*96dupTT (chr7-5527651-C-CAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001101.5(ACTB):c.*95_*96dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,326,666 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ACTB
NM_001101.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Publications

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

ACTB links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000165 (24/145470) while in subpopulation AFR AF = 0.000431 (17/39472). AF 95% confidence interval is 0.000274. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 24 AD gene.

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.95_96dupTT		3_prime_UTR	Exon 6 of 6	NP_001092.1	P60709

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTB	ENST00000646664.1	MANE Select	c.95_96dupTT	3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
ACTB	ENST00000425660.5	TSL:1	n.886_887dupTT	non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
ACTB	ENST00000425660.5	TSL:1	n.886_887dupTT	3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

145404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000406

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000273

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000455

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000389

AC:

AN:

1181196

Hom.:

Cov.:

AF XY:

0.0000356

AC XY:

AN XY:

589760

show subpopulations

African (AFR)

AF:

0.000420

AC:

AN:

26168

American (AMR)

AF:

0.0000627

AC:

AN:

31916

Ashkenazi Jewish (ASJ)

AF:

0.0000933

AC:

AN:

21446

East Asian (EAS)

AF:

0.00

AC:

AN:

35254

South Asian (SAS)

AF:

0.00

AC:

AN:

68932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3438

European-Non Finnish (NFE)

AF:

0.0000311

AC:

AN:

901246

Other (OTH)

AF:

0.0000603

AC:

AN:

49744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000165

AC:

AN:

145470

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

AN XY:

70672

show subpopulations

African (AFR)

AF:

0.000431

AC:

AN:

39472

American (AMR)

AF:

0.000273

AC:

AN:

14648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4936

South Asian (SAS)

AF:

0.00

AC:

AN:

4592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000455

AC:

AN:

65942

Other (OTH)

AF:

0.00

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.027

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-5527651-CAAAAA-CAAAAAAA

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