rs5764419

chr22-43564048-G-A

Variant summary

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

The NM_022785.4(EFCAB6):c.3421-8952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,128 control chromosomes in the GnomAD database, including 29,201 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 0.62 (29201 hom., cov: 32)
• Consequence: EFCAB6 NM_022785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB6	NM_022785.4	c.3421-8952C>T		intron_variant		ENST00000262726.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCAB6	ENST00000262726.12	c.3421-8952C>T		intron_variant		2	NM_022785.4	P1
EFCAB6	ENST00000396231.6	c.2965-8952C>T		intron_variant		1
EFCAB6	ENST00000461800.5	n.57+6039C>T		intron_variant, non_coding_transcript_variant		1
EFCAB6	ENST00000468552.1	n.1870-8952C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93758 AN: 152010 Hom.: 29174 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.617 AC: 93829 AN: 152128 Hom.: 29201 Cov.: 32 AF XY: 0.619 AC XY: 46064 AN XY: 74382

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.623

Alfa AF: 0.632 Hom.: 13884

Bravo AF: 0.621

Asia WGS AF: 0.651 AC: 2265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.7
Dann	Benign	0.33

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: rs5764419; hg19: chr22-43959928;