Genetic Variant EFCAB13:c.806-1G>A (chr17-47370436-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PVS1_ModerateBP6BA1

The NM_152347.5(EFCAB13):c.806-1G>A variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.0216 in 1,573,628 control chromosomes in the GnomAD database, including 1,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.023 ( 108 hom., cov: 32)

Exomes 𝑓: 0.021 ( 926 hom. )

Consequence

EFCAB13
NM_152347.5 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.82

Publications

10 publications found

Variant links:

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

EFCAB13 links:

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

EFCAB13-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.024640657 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BP6

Variant 17-47370436-G-A is Benign according to our data. Variant chr17-47370436-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055475.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5 link	c.806-1G>A		splice_acceptor_variant, intron_variant	Intron 10 of 24	ENST00000331493.7	NP_689560.3	Q8IY85-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7 link	c.806-1G>A		splice_acceptor_variant, intron_variant	Intron 10 of 24	1	NM_152347.5	ENSP00000332111.2		Q8IY85-1

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3436

AN:

152110

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00968

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.0601

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0331

AC:

8293

AN:

250444

AF XY:

0.0342

show subpopulations

Gnomad AFR exome

AF:

0.00956

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0231

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0331

GnomAD4 exome

AF:

0.0215

AC:

30506

AN:

1421400

Hom.:

926

Cov.:

AF XY:

0.0225

AC XY:

15978

AN XY:

709524

show subpopulations

African (AFR)

AF:

0.00802

AC:

262

AN:

32674

American (AMR)

AF:

0.0173

AC:

769

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

602

AN:

25856

East Asian (EAS)

AF:

0.170

AC:

6682

AN:

39222

South Asian (SAS)

AF:

0.0591

AC:

5026

AN:

85060

European-Finnish (FIN)

AF:

0.0157

AC:

835

AN:

53314

Middle Eastern (MID)

AF:

0.0225

AC:

128

AN:

5688

European-Non Finnish (NFE)

AF:

0.0136

AC:

14663

AN:

1076002

Other (OTH)

AF:

0.0261

AC:

1539

AN:

59034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

1223

2445

3668

4890

6113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.0226

AC:

3441

AN:

152228

Hom.:

108

Cov.:

AF XY:

0.0248

AC XY:

1847

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00970

AC:

403

AN:

41550

American (AMR)

AF:

0.0264

AC:

403

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

AN:

3470

East Asian (EAS)

AF:

0.176

AC:

909

AN:

5178

South Asian (SAS)

AF:

0.0602

AC:

290

AN:

4818

European-Finnish (FIN)

AF:

0.0148

AC:

157

AN:

10590

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0153

AC:

1040

AN:

68010

Other (OTH)

AF:

0.0298

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

164

329

493

658

822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0203

Hom.:

189

Bravo

AF:

0.0224

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0182

AC:

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0168

AC:

144

ExAC

AF:

0.0335

AC:

4061

Asia WGS

AF:

0.105

AC:

365

AN:

3474

EpiCase

AF:

0.0162

EpiControl

AF:

0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EFCAB13-related disorder

Benign:1

Sep 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.86

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Benign

0.76

PhyloP100

3.8

GERP RS

3.9

Mutation Taster

=60/40

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.80

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.80

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over