rs17123726

Positions:

• chr20-32859562-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001143967.2(EFCAB8):​c.-11+556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 152,328 control chromosomes in the GnomAD database, including 26 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 0.015 (26 hom., cov: 32)
• Consequence: EFCAB8 NM_001143967.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

EFCAB8 (HGNC:34532): (EF-hand calcium binding domain 8) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.015 (2283/152328) while in subpopulation SAS AF= 0.0437 (211/4824). AF 95% confidence interval is 0.0389. There are 26 homozygotes in gnomad4. There are 1151 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB8	NM_001143967.2	c.-11+556A>G		intron_variant		ENST00000400522.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCAB8	ENST00000400522.9	c.-11+556A>G		intron_variant		5	NM_001143967.2	P1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2288 AN: 152210 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00936

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.00909

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.00862

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

GnomAD4 genome AF: 0.0150 AC: 2283 AN: 152328 Hom.: 26 Cov.: 32 AF XY: 0.0155 AC XY: 1151 AN XY: 74486

Gnomad4 AFR AF: 0.00933

Gnomad4 AMR AF: 0.00895

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0437

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0191

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.0181 Hom.: 9

Bravo AF: 0.0130

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.083
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: rs17123726; hg19: chr20-31447368;