Genetic Variant EFCAB3:p.Lys15Asn (chr17-62373824-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001144933.2(EFCAB3):c.45G>C(p.Lys15Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,511,846 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 95 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 76 hom. )

Consequence

EFCAB3
NM_001144933.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.490

Publications

3 publications found

Variant links:

Genes affected

EFCAB3 (HGNC:26379): (EF-hand calcium binding domain 3) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022574067).

BP6

Variant 17-62373824-G-C is Benign according to our data. Variant chr17-62373824-G-C is described in ClinVar as Benign. ClinVar VariationId is 770272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144933.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	NM_001144933.2		c.45G>C	p.Lys15Asn	missense	Exon 2 of 12	NP_001138405.1	Q8N7B9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	ENST00000450662.7	TSL:5	c.45G>C	p.Lys15Asn	missense	Exon 2 of 12	ENSP00000403932.2	Q8N7B9-2
	EFCAB3	ENST00000636041.1	TSL:5	n.274G>C		non_coding_transcript_exon	Exon 4 of 14

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2939

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0673

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00434

AC:

652

AN:

150200

AF XY:

0.00321

show subpopulations

Gnomad AFR exome

AF:

0.0708

Gnomad AMR exome

AF:

0.00277

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000374

Gnomad OTH exome

AF:

0.00257

GnomAD4 exome

AF:

0.00174

AC:

2369

AN:

1359624

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

979

AN XY:

672232

show subpopulations

African (AFR)

AF:

0.0625

AC:

1889

AN:

30216

American (AMR)

AF:

0.00337

AC:

116

AN:

34374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24750

East Asian (EAS)

AF:

0.00

AC:

AN:

35250

South Asian (SAS)

AF:

0.0000390

AC:

AN:

76910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49066

Middle Eastern (MID)

AF:

0.00232

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.000125

AC:

131

AN:

1046882

Other (OTH)

AF:

0.00384

AC:

217

AN:

56574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.424

Heterozygous variant carriers

180

269

359

449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0193

AC:

2937

AN:

152222

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1412

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0671

AC:

2785

AN:

41534

American (AMR)

AF:

0.00693

AC:

106

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68014

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

133

266

399

532

665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00276

Hom.:

Bravo

AF:

0.0215

ExAC

AF:

0.00737

AC:

156

Asia WGS

AF:

0.00231

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.95

PhyloP100

0.49

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.66

REVEL

Benign

0.040

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Vest4

0.22

MutPred

0.37

Loss of ubiquitination at K15 (P = 0.0155)

MVP

0.13

MPC

0.36

ClinPred

0.056

GERP RS

0.79

gMVP

0.19

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over