chr1-245087293-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032328.4(EFCAB2):​c.422T>C​(p.Ile141Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000826 in 1,611,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

EFCAB2
NM_032328.4 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96
Variant links:
Genes affected
EFCAB2 (HGNC:28166): (EF-hand calcium binding domain 2) The gene encodes a protein that contains two EF-hand calcium-binding domains although its function has yet to be determined. Alternatively spliced transcripts have been observed. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.030481607).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EFCAB2NM_032328.4 linkc.422T>C p.Ile141Thr missense_variant Exon 8 of 8 ENST00000366523.6 NP_115704.1 Q5VUJ9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EFCAB2ENST00000366523.6 linkc.422T>C p.Ile141Thr missense_variant Exon 8 of 8 3 NM_032328.4 ENSP00000355480.1 Q5VUJ9-2

Frequencies

GnomAD3 genomes
AF:
0.000368
AC:
56
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00135
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD3 exomes
AF:
0.000117
AC:
29
AN:
247778
Hom.:
0
AF XY:
0.0000969
AC XY:
13
AN XY:
134182
show subpopulations
Gnomad AFR exome
AF:
0.00167
Gnomad AMR exome
AF:
0.0000304
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000521
AC:
76
AN:
1458770
Hom.:
0
Cov.:
31
AF XY:
0.0000441
AC XY:
32
AN XY:
725770
show subpopulations
Gnomad4 AFR exome
AF:
0.00192
Gnomad4 AMR exome
AF:
0.0000231
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000374
AC:
57
AN:
152346
Hom.:
0
Cov.:
33
AF XY:
0.000389
AC XY:
29
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00137
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000499
Hom.:
0
Bravo
AF:
0.000570
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000132
AC:
16

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.422T>C (p.I141T) alteration is located in exon 8 (coding exon 7) of the EFCAB2 gene. This alteration results from a T to C substitution at nucleotide position 422, causing the isoleucine (I) at amino acid position 141 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Benign
0.97
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.022
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.030
T
MetaSVM
Benign
-0.86
T
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-2.2
N
REVEL
Uncertain
0.30
Sift
Benign
0.17
T
Sift4G
Benign
0.70
T
Polyphen
0.029
B
Vest4
0.26
MVP
0.76
MPC
0.18
ClinPred
0.049
T
GERP RS
4.5
gMVP
0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376666673; hg19: chr1-245250595; API