dbSNP rs6665021: EFCAB14:p.Leu337Pro (chr1-46686848-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_014774.3(EFCAB14):c.1010T>C(p.Leu337Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000966 in 1,613,808 control chromosomes in the GnomAD database, including 14 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 0.0051 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 6 hom. )

Consequence

EFCAB14
NM_014774.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Publications

4 publications found

Variant links:

Genes affected

EFCAB14 (HGNC:29051): (EF-hand calcium binding domain 14) Predicted to enable calcium ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB14 links:

EFCAB14-AS1 (HGNC:44108): (EFCAB14 antisense RNA 1)

EFCAB14-AS1 links:

LOC105378698 (HGNC:):

LOC105378698 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00832662).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00511 (779/152348) while in subpopulation AFR AF = 0.0175 (729/41586). AF 95% confidence interval is 0.0165. There are 8 homozygotes in GnomAd4. There are 384 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
EFCAB14	NM_014774.3 link	c.1010T>C	p.Leu337Pro	missense_variant	Exon 8 of 11	ENST00000371933.8	NP_055589.1
EFCAB14-AS1	NR_038827.1 link	n.359+85A>G		intron_variant	Intron 3 of 3
EFCAB14-AS1	NR_038828.1 link	n.275+85A>G		intron_variant	Intron 2 of 2
LOC105378698	XR_947298.3 link	n.-71T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB14	ENST00000371933.8 link	c.1010T>C	p.Leu337Pro	missense_variant	Exon 8 of 11	1	NM_014774.3	ENSP00000361001.3

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

781

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

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:

0.00143

GnomAD2 exomes

AF:

0.00138

AC:

347

AN:

251030

AF XY:

0.000966

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000534

AC:

780

AN:

1461460

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

332

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.0197

AC:

660

AN:

33444

American (AMR)

AF:

0.000851

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1111778

Other (OTH)

AF:

0.00103

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00511

AC:

779

AN:

152348

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

384

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0175

AC:

729

AN:

41586

American (AMR)

AF:

0.00307

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00196

Hom.:

Bravo

AF:

0.00564

ESP6500AA

AF:

0.0197

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00168

AC:

204

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0083

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.5

PhyloP100

2.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.39

Sift

Benign

0.073

Sift4G

Benign

0.25

Polyphen

1.0

Vest4

0.25

MVP

0.79

MPC

0.24

ClinPred

0.051

GERP RS

4.5

Varity_R

0.61

gMVP

0.28

Mutation Taster

=69/31

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over