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GeneBe

1-169596008-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_003005.4(SELP):c.2018A>G(p.Asn673Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,926 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. N673N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0059 ( 10 hom., cov: 32)
Exomes 𝑓: 0.00060 ( 9 hom. )

Consequence

SELP
NM_003005.4 missense

Scores

1
16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.97
Variant links:
Genes affected
SELP (HGNC:10721): (selectin P) This gene encodes a 140 kDa protein that is stored in the alpha-granules of platelets and Weibel-Palade bodies of endothelial cells. This protein redistributes to the plasma membrane during platelet activation and degranulation and mediates the interaction of activated endothelial cells or platelets with leukocytes. The membrane protein is a calcium-dependent receptor that binds to sialylated forms of Lewis blood group carbohydrate antigens on neutrophils and monocytes. Alternative splice variants may occur but are not well documented. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 1-169596008-T-C is Benign according to our data. Variant chr1-169596008-T-C is described in ClinVar as [Benign]. Clinvar id is 782395.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00595 (906/152292) while in subpopulation AFR AF= 0.0211 (877/41560). AF 95% confidence interval is 0.0199. There are 10 homozygotes in gnomad4. There are 444 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELPNM_003005.4 linkuse as main transcriptc.2018A>G p.Asn673Ser missense_variant 12/17 ENST00000263686.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELPENST00000263686.11 linkuse as main transcriptc.2018A>G p.Asn673Ser missense_variant 12/171 NM_003005.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00595
AC:
906
AN:
152174
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0212
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00148
AC:
373
AN:
251378
Hom.:
2
AF XY:
0.000979
AC XY:
133
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.0207
Gnomad AMR exome
AF:
0.000723
Gnomad ASJ exome
AF:
0.000595
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000600
AC:
877
AN:
1461634
Hom.:
9
Cov.:
31
AF XY:
0.000487
AC XY:
354
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.0209
Gnomad4 AMR exome
AF:
0.000805
Gnomad4 ASJ exome
AF:
0.000766
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.00141
GnomAD4 genome
AF:
0.00595
AC:
906
AN:
152292
Hom.:
10
Cov.:
32
AF XY:
0.00596
AC XY:
444
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0211
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.00122
Hom.:
1
Bravo
AF:
0.00668
ESP6500AA
AF:
0.0197
AC:
87
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00158
AC:
192
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.50
Cadd
Benign
20
Dann
Benign
0.80
DEOGEN2
Benign
0.017
T;.;T;T;T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.52
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.32
T;T;T;T;T
MetaRNN
Benign
0.0044
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.1
N;N;N;.;N
REVEL
Benign
0.14
Sift
Benign
0.64
T;T;T;.;T
Sift4G
Benign
0.65
T;T;T;T;T
Vest4
0.14, 0.17, 0.17, 0.17
MVP
0.67
MPC
0.050
ClinPred
0.0072
T
GERP RS
4.2
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.77
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.77
Position offset: -1

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: rs3917815; hg19: chr1-169565246; COSMIC: COSV55251401; COSMIC: COSV55251401; API