Genetic Variant NM_022496.5:c.572+92T>G (chr12-100210443-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_022496.5(ACTR6):c.572+92T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,330,016 control chromosomes in the GnomAD database, including 40,316 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 0.32 ( 11615 hom., cov: 32)

Exomes 𝑓: 0.20 ( 28701 hom. )

Consequence

ACTR6
NM_022496.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

6 publications found

Variant links:

Genes affected

ACTR6 (HGNC:24025): (actin related protein 6) Predicted to enable nucleosome binding activity. Predicted to be involved in histone exchange. Predicted to be located in nucleus. Predicted to be part of Swr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACTR6 links:

DEPDC4 (HGNC:22952): (DEP domain containing 4) Predicted to be involved in intracellular signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC4 links:

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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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022496.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACTR6	NM_022496.5	MANE Select	c.572+92T>G	intron	N/A	NP_071941.1
ACTR6	NR_048568.2		n.750+92T>G	intron	N/A
ACTR6	NR_048569.2		n.622+92T>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACTR6	ENST00000188312.7	TSL:1 MANE Select	c.572+92T>G	intron	N/A	ENSP00000188312.2
ACTR6	ENST00000553038.5	TSL:1	n.*52+92T>G	intron	N/A	ENSP00000447641.1
ACTR6	ENST00000552376.5	TSL:5	c.572+92T>G	intron	N/A	ENSP00000447237.1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49103

AN:

151770

Hom.:

11572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.0602

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.205

AC:

240929

AN:

1178130

Hom.:

28701

AF XY:

0.203

AC XY:

120915

AN XY:

595406

show subpopulations

African (AFR)

AF:

0.685

AC:

18795

AN:

27456

American (AMR)

AF:

0.156

AC:

5723

AN:

36708

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

5406

AN:

21936

East Asian (EAS)

AF:

0.0560

AC:

2117

AN:

37788

South Asian (SAS)

AF:

0.199

AC:

14754

AN:

74294

European-Finnish (FIN)

AF:

0.165

AC:

8008

AN:

48490

Middle Eastern (MID)

AF:

0.258

AC:

1145

AN:

4438

European-Non Finnish (NFE)

AF:

0.198

AC:

173738

AN:

876676

Other (OTH)

AF:

0.223

AC:

11243

AN:

50344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

8586

17172

25759

34345

42931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5764

11528

17292

23056

28820

<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:

0.324

AC:

49201

AN:

151886

Hom.:

11615

Cov.:

AF XY:

0.316

AC XY:

23469

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.670

AC:

27753

AN:

41420

American (AMR)

AF:

0.223

AC:

3401

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

819

AN:

3462

East Asian (EAS)

AF:

0.0600

AC:

310

AN:

5170

South Asian (SAS)

AF:

0.185

AC:

891

AN:

4814

European-Finnish (FIN)

AF:

0.169

AC:

1778

AN:

10538

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13234

AN:

67938

Other (OTH)

AF:

0.287

AC:

604

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1326

2652

3979

5305

6631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.230

Hom.:

21915

Bravo

AF:

0.344

Asia WGS

AF:

0.192

AC:

668

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.1

(source)

DANN

Benign

0.37

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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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