rs8123073

chr20-32859052-A-Gchr20-32859052-A-T

Variant summary

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

The NM_001143967.2(EFCAB8):c.-11+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 470,962 control chromosomes in the GnomAD database, including 780 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 0.058 (533 hom., cov: 32)
  • Exomes 𝑓: 0.026 (247 hom.)
• Consequence: EFCAB8 NM_001143967.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB8	NM_001143967.2	c.-11+46A>G		intron_variant		ENST00000400522.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCAB8	ENST00000400522.9	c.-11+46A>G		intron_variant		5	NM_001143967.2	P1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8819 AN: 152098 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0325

GnomAD3 exomes AF: 0.0258 AC: 3904 AN: 151140 Hom.: 141 AF XY: 0.0257 AC XY: 2087 AN XY: 81170

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00203

Gnomad EAS exome AF: 0.00223

Gnomad SAS exome AF: 0.0436

Gnomad FIN exome AF: 0.0162

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0167

GnomAD4 exome AF: 0.0261 AC: 8320 AN: 318746 Hom.: 247 Cov.: 0 AF XY: 0.0262 AC XY: 4715 AN XY: 180064

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.00297

Gnomad4 EAS exome AF: 0.00206

Gnomad4 SAS exome AF: 0.0399

Gnomad4 FIN exome AF: 0.0160

Gnomad4 NFE exome AF: 0.0211

Gnomad4 OTH exome AF: 0.0256

GnomAD4 genome AF: 0.0580 AC: 8833 AN: 152216 Hom.: 533 Cov.: 32 AF XY: 0.0575 AC XY: 4277 AN XY: 74424

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0255 Hom.: 53

Bravo AF: 0.0617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.5
Dann	Benign	0.72

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: rs8123073; hg19: chr20-31446858; COSMIC: COSV68701132; COSMIC: COSV68701132;