22-43683558-A-T

Position:

• chr22-43683558-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EFCAB6	NM_022785.4	c.1251+189T>A		intron_variant		ENST00000262726.12	NP_073622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB6	ENST00000262726.12	c.1251+189T>A		intron_variant		2	NM_022785.4	ENSP00000262726.7
EFCAB6	ENST00000396231.6	c.795+189T>A		intron_variant		1		ENSP00000379533.2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67921 AN: 151930 Hom.: 15598 Cov.: 32

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

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.447 AC: 67971 AN: 152048 Hom.: 15613 Cov.: 32 AF XY: 0.444 AC XY: 32974 AN XY: 74330

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.432

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
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs2071716; hg19: chr22-44079438;