dbSNP rs1474445: ENSG00000272719:n.488A>G (chr7-5557218-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000609813.1(ENSG00000272719):n.488A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,228 control chromosomes in the GnomAD database, including 3,665 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3665 hom., cov: 32)

Exomes 𝑓: 0.27 ( 0 hom. )

Consequence

ENSG00000272719
ENST00000609813.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.471

Publications

6 publications found

Variant links:

Genes affected

ENSG00000272719 (HGNC:):

ENSG00000272719 links:

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: ClinGen, Orphanet
Baraitser-Winter syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, G2P
developmental malformations-deafness-dystonia syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina
ACTB-associated syndromic thrombocytopenia
Inheritance: AD Classification: MODERATE Submitted by: ClinGen, Ambry Genetics

ACTB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000272719	ENST00000609813.1 link	n.488A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
ACTB	ENST00000675515.1 link	c.-7+6496T>C	intron_variant	Intron 1 of 5		ENSP00000501862.1	P60709
ACTB	ENST00000443528.5 link	c.-7+5356T>C	intron_variant	Intron 1 of 2	4	ENSP00000393951.1	C9JZR7
ACTB	ENST00000414620.1 link	c.-103+5356T>C	intron_variant	Intron 1 of 3	4	ENSP00000401032.1	C9JTX5

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32670

AN:

152082

Hom.:

3672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.269

AC:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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:

0.215

AC:

32685

AN:

152202

Hom.:

3665

Cov.:

AF XY:

0.221

AC XY:

16474

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.225

AC:

9326

AN:

41534

American (AMR)

AF:

0.183

AC:

2798

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

820

AN:

3468

East Asian (EAS)

AF:

0.171

AC:

886

AN:

5188

South Asian (SAS)

AF:

0.281

AC:

1359

AN:

4828

European-Finnish (FIN)

AF:

0.318

AC:

3368

AN:

10580

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13475

AN:

68020

Other (OTH)

AF:

0.208

AC:

439

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1361

2722

4083

5444

6805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.195

Hom.:

4177

Bravo

AF:

0.200

Asia WGS

AF:

0.230

AC:

798

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

(source)

DANN

Benign

0.85

PhyloP100

0.47

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over