rs8140172

Positions:

• chr22-43808439-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.-8+556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,198 control chromosomes in the GnomAD database, including 2,246 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 0.10 (2246 hom., cov: 32)
• Consequence: EFCAB6 NM_022785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476

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 (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB6	NM_022785.4	c.-8+556G>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.-8+556G>A		intron_variant		2	NM_022785.4	ENSP00000262726.7

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15348 AN: 152078 Hom.: 2237 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.101 AC: 15410 AN: 152198 Hom.: 2246 Cov.: 32 AF XY: 0.0973 AC XY: 7242 AN XY: 74430

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00953

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0516 Hom.: 387

Bravo AF: 0.114

Asia WGS AF: 0.0290 AC: 100 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	0.80
DANN	Benign	0.67

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: rs8140172; hg19: chr22-44204319;