22-43700802-T-C

Position:

• chr22-43700802-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB6	NM_022785.4	c.1031+10673A>G		intron_variant		ENST00000262726.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCAB6	ENST00000262726.12	c.1031+10673A>G		intron_variant		2	NM_022785.4	P1
EFCAB6	ENST00000396231.6	c.575+10673A>G		intron_variant		1
EFCAB6	ENST00000404038.5	n.1345+10673A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.247

Alfa AF: 0.236 Hom.: 633

Bravo AF: 0.233

Asia WGS AF: 0.363 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.55

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: rs970865; hg19: chr22-44096682;