Genetic Variant EFCAB6:c.1251+189T>A (chr22-43683558-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_022785.4(EFCAB6):c.1251+189T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 571,600 control chromosomes in the GnomAD database, including 54,621 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 0.45 ( 15613 hom., cov: 32)

Exomes 𝑓: 0.42 ( 39008 hom. )

Consequence

EFCAB6
NM_022785.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

Publications

4 publications found

Variant links:

Genes affected

EFCAB6 (HGNC:24204): (EF-hand calcium binding domain 6) This gene encodes a protein which directly binds the oncogene DJ-1 and androgen receptor to form a ternary complex in cells. This binding protein recruits histone-deacetylase complexes in order to repress transcription activity of androgen receptor. This protein may also play a role in spermatogenesis and fertilization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

EFCAB6 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022785.4. 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
	EFCAB6	NM_022785.4	MANE Select	c.1251+189T>A		intron	N/A	NP_073622.2
	EFCAB6	NM_198856.3		c.795+189T>A		intron	N/A	NP_942153.1	Q5THR3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFCAB6	ENST00000262726.12	TSL:2 MANE Select	c.1251+189T>A	intron	N/A	ENSP00000262726.7	Q5THR3-1
EFCAB6	ENST00000396231.6	TSL:1	c.795+189T>A	intron	N/A	ENSP00000379533.2	Q5THR3-2
EFCAB6	ENST00000970826.1		c.1251+189T>A	intron	N/A	ENSP00000640885.1

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67921

AN:

151930

Hom.:

15598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.431

GnomAD4 exome

AF:

0.423

AC:

177588

AN:

419552

Hom.:

39008

AF XY:

0.426

AC XY:

93665

AN XY:

220044

show subpopulations

African (AFR)

AF:

0.518

AC:

6235

AN:

12046

American (AMR)

AF:

0.284

AC:

5056

AN:

17802

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

5658

AN:

12940

East Asian (EAS)

AF:

0.226

AC:

6868

AN:

30342

South Asian (SAS)

AF:

0.458

AC:

17594

AN:

38404

European-Finnish (FIN)

AF:

0.405

AC:

11961

AN:

29530

Middle Eastern (MID)

AF:

0.447

AC:

826

AN:

1846

European-Non Finnish (NFE)

AF:

0.448

AC:

112882

AN:

252206

Other (OTH)

AF:

0.430

AC:

10508

AN:

24436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4554

9108

13661

18215

22769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.447

AC:

67971

AN:

152048

Hom.:

15613

Cov.:

AF XY:

0.444

AC XY:

32974

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.523

AC:

21673

AN:

41444

American (AMR)

AF:

0.350

AC:

5354

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1484

AN:

3468

East Asian (EAS)

AF:

0.231

AC:

1194

AN:

5170

South Asian (SAS)

AF:

0.456

AC:

2194

AN:

4808

European-Finnish (FIN)

AF:

0.394

AC:

4161

AN:

10566

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.448

AC:

30469

AN:

67990

Other (OTH)

AF:

0.432

AC:

910

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1920

3840

5761

7681

9601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.436

Hom.:

1778

Bravo

AF:

0.442

Asia WGS

AF:

0.370

AC:

1285

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.0

(source)

DANN

Benign

0.84

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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