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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB6	NM_022785.4 link	c.1251+189T>A		intron_variant	Intron 12 of 31	ENST00000262726.12	NP_073622.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EFCAB6	ENST00000262726.12 link	c.1251+189T>A	intron_variant	Intron 12 of 31	2	NM_022785.4	ENSP00000262726.7
EFCAB6	ENST00000396231.6 link	c.795+189T>A	intron_variant	Intron 10 of 29	1		ENSP00000379533.2
EFCAB6	ENST00000404038.5 link	n.*106T>A	downstream_gene_variant		2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over