Genetic Variant EFCAB8:c.-11+46A>G (chr20-32859052-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

Publications

8 publications found

Variant links:

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]

EFCAB8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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>G		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>G		intron	N/A	ENSP00000383366.5

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8819

AN:

152098

Hom.:

532

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0258

AC:

3904

AN:

151140

AF XY:

0.0257

show subpopulations

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 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.:

AF XY:

0.0262

AC XY:

4715

AN XY:

180064

show subpopulations

African (AFR)

AF:

0.160

AC:

1383

AN:

8624

American (AMR)

AF:

0.0125

AC:

340

AN:

27276

Ashkenazi Jewish (ASJ)

AF:

0.00297

AC:

AN:

10786

East Asian (EAS)

AF:

0.00206

AC:

AN:

9208

South Asian (SAS)

AF:

0.0399

AC:

2385

AN:

59706

European-Finnish (FIN)

AF:

0.0160

AC:

434

AN:

27088

Middle Eastern (MID)

AF:

0.00360

AC:

AN:

2780

European-Non Finnish (NFE)

AF:

0.0211

AC:

3351

AN:

158962

Other (OTH)

AF:

0.0256

AC:

366

AN:

14316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

416

832

1249

1665

2081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0580

AC:

8833

AN:

152216

Hom.:

533

Cov.:

AF XY:

0.0575

AC XY:

4277

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.160

AC:

6652

AN:

41508

American (AMR)

AF:

0.0233

AC:

357

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00232

AC:

AN:

5176

South Asian (SAS)

AF:

0.0442

AC:

213

AN:

4824

European-Finnish (FIN)

AF:

0.0166

AC:

176

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0193

AC:

1312

AN:

68018

Other (OTH)

AF:

0.0322

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

390

780

1170

1560

1950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0629

Hom.:

315

Bravo

AF:

0.0617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.5

(source)

DANN

Benign

0.72

PhyloP100

0.12

PromoterAI

0.0079

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over