chr22-43684766-C-T

Position:

• chr22-43684766-C-T

Variant summary

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

The NM_022785.4(EFCAB6):​c.1143-911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,134 control chromosomes in the GnomAD database, including 5,103 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 0.23 (5103 hom., cov: 33)
• Consequence: EFCAB6 NM_022785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB6	NM_022785.4	c.1143-911G>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.1143-911G>A		intron_variant		2	NM_022785.4	ENSP00000262726.7
EFCAB6	ENST00000396231.6	c.687-911G>A		intron_variant		1		ENSP00000379533.2
EFCAB6	ENST00000404038.5	n.1457-911G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34287 AN: 152016 Hom.: 5099 Cov.: 33

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34301 AN: 152134 Hom.: 5103 Cov.: 33 AF XY: 0.234 AC XY: 17362 AN XY: 74340

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.244

Alfa AF: 0.252 Hom.: 1399

Bravo AF: 0.232

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.60

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: rs9306469; hg19: chr22-44080646;