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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFCAB14	NM_014774.3	MANE Select	c.1010T>C	p.Leu337Pro	missense	Exon 8 of 11	NP_055589.1	O75071
EFCAB14-AS1	NR_038827.1		n.359+85A>G		intron	N/A
EFCAB14-AS1	NR_038828.1		n.275+85A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFCAB14	ENST00000371933.8	TSL:1 MANE Select	c.1010T>C	p.Leu337Pro	missense	Exon 8 of 11	ENSP00000361001.3	O75071
EFCAB14	ENST00000672422.2		c.1103T>C	p.Leu368Pro	missense	Exon 8 of 11	ENSP00000499873.2	A0A804H3B5
EFCAB14	ENST00000674263.1		c.1010T>C	p.Leu337Pro	missense	Exon 8 of 12	ENSP00000501323.1	A0A6I8PIF8

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over