2-27079228-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007046.4(EMILIN1):​c.163C>T​(p.Arg55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,410,802 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

EMILIN1
NM_007046.4 missense

Scores

2
13
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.514

Publications

2 publications found
Variant links:
Genes affected
EMILIN1 (HGNC:19880): (elastin microfibril interfacer 1) This gene encodes an extracellular matrix glycoprotein that is characterized by an N-terminal microfibril interface domain, a coiled-coiled alpha-helical domain, a collagenous domain and a C-terminal globular C1q domain. The encoded protein associates with elastic fibers at the interface between elastin and microfibrils and may play a role in the development of elastic tissues including large blood vessels, dermis, heart and lung. [provided by RefSeq, Sep 2009]
EMILIN1 Gene-Disease associations (from GenCC):
  • neuronopathy, distal hereditary motor, autosomal dominant 10
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EMILIN1NM_007046.4 linkc.163C>T p.Arg55Cys missense_variant Exon 1 of 8 ENST00000380320.9 NP_008977.1 Q9Y6C2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EMILIN1ENST00000380320.9 linkc.163C>T p.Arg55Cys missense_variant Exon 1 of 8 1 NM_007046.4 ENSP00000369677.4 Q9Y6C2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000543
AC:
1
AN:
184042
AF XY:
0.00000958
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000119
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000284
AC:
4
AN:
1410802
Hom.:
0
Cov.:
31
AF XY:
0.00000142
AC XY:
1
AN XY:
702134
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28692
American (AMR)
AF:
0.00
AC:
0
AN:
33542
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24150
East Asian (EAS)
AF:
0.0000287
AC:
1
AN:
34806
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81340
European-Finnish (FIN)
AF:
0.0000194
AC:
1
AN:
51480
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5590
European-Non Finnish (NFE)
AF:
9.15e-7
AC:
1
AN:
1093216
Other (OTH)
AF:
0.0000172
AC:
1
AN:
57986
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.588
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
ExAC
AF:
0.0000167
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Uncertain
0.060
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.64
D
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.86
D
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.48
T
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
0.69
N
PhyloP100
0.51
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-4.2
D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.032
D
Polyphen
1.0
D
Vest4
0.44
MutPred
0.47
Loss of solvent accessibility (P = 8e-04);
MVP
0.88
MPC
0.52
ClinPred
0.88
D
GERP RS
3.9
Varity_R
0.14
gMVP
0.70
Mutation Taster
=78/22
polymorphism

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

Other links and lift over

dbSNP: rs758148332; hg19: chr2-27302096; COSMIC: COSV107500276; COSMIC: COSV107500276; API