Genetic Variant ACTR6:n.*542-3714A>G (chr12-100238019-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 ENST00000553038.5(ACTR6):n.*542-3714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 969,742 control chromosomes in the GnomAD database, including 11,776 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 0.16 ( 2803 hom., cov: 31)

Exomes 𝑓: 0.14 ( 8973 hom. )

Consequence

ACTR6
ENST00000553038.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.418

Publications

9 publications found

Variant links:

COSMIC-nc: COSV107487672

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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553038.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEPDC4	NM_001387205.1	c.1552T>C	p.Ter518Glnext*?	stop_lost	Exon 9 of 9	NP_001374134.1
DEPDC4	NM_001387206.1	c.1552T>C	p.Ter518Glnext*?	stop_lost	Exon 9 of 10	NP_001374135.1
DEPDC4	NM_001387210.1	c.1009T>C	p.Ter337Glnext*?	stop_lost	Exon 7 of 7	NP_001374139.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACTR6	ENST00000553038.5	TSL:1	n.*542-3714A>G	intron	N/A	ENSP00000447641.1
DEPDC4	ENST00000378244.6	TSL:2	n.*648T>C	non_coding_transcript_exon	Exon 9 of 11	ENSP00000367490.2
DEPDC4	ENST00000549100.5	TSL:3	n.282T>C	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24296

AN:

151880

Hom.:

2803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.600

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.165

GnomAD4 exome

AF:

0.139

AC:

114036

AN:

817744

Hom.:

8973

Cov.:

AF XY:

0.139

AC XY:

52737

AN XY:

378186

show subpopulations

African (AFR)

AF:

0.0742

AC:

1151

AN:

15516

American (AMR)

AF:

0.273

AC:

264

AN:

966

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

810

AN:

5062

East Asian (EAS)

AF:

0.603

AC:

2119

AN:

3512

South Asian (SAS)

AF:

0.308

AC:

4933

AN:

16034

European-Finnish (FIN)

AF:

0.239

AC:

AN:

272

Middle Eastern (MID)

AF:

0.138

AC:

219

AN:

1586

European-Non Finnish (NFE)

AF:

0.134

AC:

100029

AN:

748028

Other (OTH)

AF:

0.166

AC:

4446

AN:

26768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

3633

7266

10899

14532

18165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5074

10148

15222

20296

25370

<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:

0.160

AC:

24298

AN:

151998

Hom.:

2803

Cov.:

AF XY:

0.173

AC XY:

12887

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.0703

AC:

2918

AN:

41514

American (AMR)

AF:

0.232

AC:

3531

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

555

AN:

3468

East Asian (EAS)

AF:

0.600

AC:

3077

AN:

5128

South Asian (SAS)

AF:

0.329

AC:

1583

AN:

4816

European-Finnish (FIN)

AF:

0.243

AC:

2565

AN:

10554

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9568

AN:

67960

Other (OTH)

AF:

0.163

AC:

342

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

956

1911

2867

3822

4778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.149

Hom.:

6347

Bravo

AF:

0.154

Asia WGS

AF:

0.411

AC:

1427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.67

(source)

DANN

Benign

0.32

PhyloP100

-0.42

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over