22-43700802-T-C

Variant names:

• chr22-43700802-T-C
• rs970865
• NM_022785.4:c.1031+10673A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022785.4(EFCAB6):​c.1031+10673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,184 control chromosomes in the GnomAD database, including 5,151 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 (5151 hom., cov: 32)
• Consequence: EFCAB6 NM_022785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 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.1031+10673A>G		intron	N/A	NP_073622.2
	EFCAB6	NM_198856.3		c.575+10673A>G		intron	N/A	NP_942153.1	Q5THR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB6	ENST00000262726.12	TSL:2 MANE Select	c.1031+10673A>G		intron	N/A	ENSP00000262726.7	Q5THR3-1
	EFCAB6	ENST00000396231.6	TSL:1	c.575+10673A>G		intron	N/A	ENSP00000379533.2	Q5THR3-2
	EFCAB6	ENST00000970826.1		c.1031+10673A>G		intron	N/A	ENSP00000640885.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34525 AN: 152064 Hom.: 5146 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.227 AC: 34540 AN: 152184 Hom.: 5151 Cov.: 32 AF XY: 0.235 AC XY: 17489 AN XY: 74384

African (AFR) AF: 0.0713 AC: 2961 AN: 41554

American (AMR) AF: 0.373 AC: 5695 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3462

East Asian (EAS) AF: 0.614 AC: 3180 AN: 5176

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4812

European-Finnish (FIN) AF: 0.326 AC: 3453 AN: 10582

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16297 AN: 68002

Other (OTH) AF: 0.247 AC: 523 AN: 2114

Alfa AF: 0.230 Hom.: 637

Bravo AF: 0.233

Asia WGS AF: 0.363 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.55
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs970865; hg19: chr22-44096682;