rs9614174

Positions:

• chr22-43686574-A-C

Variant summary

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

The NM_022785.4(EFCAB6):​c.1142+897T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,242 control chromosomes in the GnomAD database, including 1,200 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 0.11 (1200 hom., cov: 33)
• Consequence: EFCAB6 NM_022785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB6	NM_022785.4	c.1142+897T>G		intron_variant		ENST00000262726.12	NP_073622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB6	ENST00000262726.12	c.1142+897T>G		intron_variant		2	NM_022785.4	ENSP00000262726	P1
EFCAB6	ENST00000396231.6	c.686+897T>G		intron_variant		1		ENSP00000379533
EFCAB6	ENST00000404038.5	n.1456+897T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16491 AN: 152124 Hom.: 1202 Cov.: 33

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0566

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.108 AC: 16480 AN: 152242 Hom.: 1200 Cov.: 33 AF XY: 0.105 AC XY: 7794 AN XY: 74434

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.00522

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.123

Alfa AF: 0.153 Hom.: 2454

Bravo AF: 0.107

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.80
DANN	Benign	0.49

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: rs9614174; hg19: chr22-44082454;