NM_000450.2:c.770A>C

Variant summary

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

The NM_000450.2(SELE):​c.770A>C​(p.Gln257Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,614,152 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0065 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

SELE
NM_000450.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.328

Publications

8 publications found
Variant links:
Genes affected
SELE (HGNC:10718): (selectin E) The protein encoded by this gene is found in cytokine-stimulated endothelial cells and is thought to be responsible for the accumulation of blood leukocytes at sites of inflammation by mediating the adhesion of cells to the vascular lining. It exhibits structural features such as the presence of lectin- and EGF-like domains followed by short consensus repeat (SCR) domains that contain 6 conserved cysteine residues. These proteins are part of the selectin family of cell adhesion molecules. Adhesion molecules participate in the interaction between leukocytes and the endothelium and appear to be involved in the pathogenesis of atherosclerosis. [provided by RefSeq, Jul 2008]
FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

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=0.0039951503).
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00655 (997/152306) while in subpopulation AFR AF = 0.0228 (947/41560). AF 95% confidence interval is 0.0216. There are 9 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SELENM_000450.2 linkc.770A>C p.Gln257Pro missense_variant Exon 6 of 14 ENST00000333360.12 NP_000441.2 P16581

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELEENST00000333360.12 linkc.770A>C p.Gln257Pro missense_variant Exon 6 of 14 1 NM_000450.2 ENSP00000331736.7 P16581

Frequencies

GnomAD3 genomes
AF:
0.00655
AC:
997
AN:
152188
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0229
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00210
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00527
GnomAD2 exomes
AF:
0.00186
AC:
466
AN:
251140
AF XY:
0.00149
show subpopulations
Gnomad AFR exome
AF:
0.0243
Gnomad AMR exome
AF:
0.00121
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000220
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000725
AC:
1060
AN:
1461846
Hom.:
12
Cov.:
32
AF XY:
0.000655
AC XY:
476
AN XY:
727224
show subpopulations
African (AFR)
AF:
0.0230
AC:
770
AN:
33476
American (AMR)
AF:
0.00130
AC:
58
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.0000464
AC:
4
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00139
AC:
8
AN:
5768
European-Non Finnish (NFE)
AF:
0.000110
AC:
122
AN:
1111976
Other (OTH)
AF:
0.00162
AC:
98
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.480
Heterozygous variant carriers
0
59
117
176
234
293
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
26
52
78
104
130
<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:
0.00655
AC:
997
AN:
152306
Hom.:
9
Cov.:
32
AF XY:
0.00658
AC XY:
490
AN XY:
74474
show subpopulations
African (AFR)
AF:
0.0228
AC:
947
AN:
41560
American (AMR)
AF:
0.00209
AC:
32
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0000735
AC:
5
AN:
68034
Other (OTH)
AF:
0.00521
AC:
11
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
53
106
158
211
264
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00407
Hom.:
12
Bravo
AF:
0.00768
ESP6500AA
AF:
0.0204
AC:
90
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00220
AC:
267
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
0.0010
DANN
Benign
0.38
DEOGEN2
Benign
0.018
.;T;T;T;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.22
T;T;T;T;T
MetaRNN
Benign
0.0040
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.40
.;.;.;N;.
PhyloP100
-0.33
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.7
N;N;N;N;N
REVEL
Benign
0.18
Sift
Benign
0.13
T;T;T;T;T
Sift4G
Benign
0.22
T;T;T;T;T
Polyphen
0.0
.;.;.;B;.
Vest4
0.12
MVP
0.32
MPC
0.066
ClinPred
0.018
T
GERP RS
-11
gMVP
0.82
Mutation Taster
=96/4
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: rs3917422; hg19: chr1-169698760; API