20-32859052-A-T

Variant names:

• chr20-32859052-A-T
• rs8123073
• NM_001143967.2:c.-11+46A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001143967.2(EFCAB8):​c.-11+46A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 470,990 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: EFCAB8 NM_001143967.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 8 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143967.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB8	NM_001143967.2	MANE Select	c.-11+46A>T		intron	N/A	NP_001137439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB8	ENST00000400522.9	TSL:5 MANE Select	c.-11+46A>T		intron	N/A	ENSP00000383366.5

Frequencies

GnomAD3 genomes AF: 0.000546 AC: 83 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000126 AC: 19 AN: 151140 AF XY: 0.000111

Gnomad AFR exome AF: 0.00237

Gnomad AMR exome AF: 0.0000817

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000722 AC: 23 AN: 318756 Hom.: 0 Cov.: 0 AF XY: 0.0000555 AC XY: 10 AN XY: 180064

African (AFR) AF: 0.00197 AC: 17 AN: 8626

American (AMR) AF: 0.000183 AC: 5 AN: 27276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10786

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.0000167 AC: 1 AN: 59710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158964

Other (OTH) AF: 0.00 AC: 0 AN: 14316

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.000672 AC XY: 50 AN XY: 74430

African (AFR) AF: 0.00200 AC: 83 AN: 41522

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		0.12
PromoterAI		0.017	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8123073; hg19: chr20-31446858;