NM_022785.4:c.-8+556G>A

Variant names:

• chr22-43808439-C-T
• rs8140172
• NM_022785.4:c.-8+556G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB6	NM_022785.4	c.-8+556G>A		intron_variant	Intron 2 of 31	ENST00000262726.12	NP_073622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB6	ENST00000262726.12	c.-8+556G>A		intron_variant	Intron 2 of 31	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

African (AFR) AF: 0.323 AC: 13385 AN: 41464

American (AMR) AF: 0.0413 AC: 632 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4828

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1038 AN: 68028

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0838 Hom.: 1766

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
PhyloP100		-0.48
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: rs8140172; hg19: chr22-44204319;