17-1745208-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000934.4(SERPINF2):​c.97C>T​(p.Arg33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,553,220 control chromosomes in the GnomAD database, including 41,715 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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.

Frequency

Genomes: 𝑓 0.23 ( 3590 hom., cov: 26)
Exomes 𝑓: 0.23 ( 38125 hom. )

Consequence

SERPINF2
NM_000934.4 missense

Scores

1
17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.790
Variant links:
Genes affected
SERPINF2 (HGNC:9075): (serpin family F member 2) This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004112065).
BP6
Variant 17-1745208-C-T is Benign according to our data. Variant chr17-1745208-C-T is described in ClinVar as [Benign]. Clinvar id is 256837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SERPINF2NM_000934.4 linkuse as main transcriptc.97C>T p.Arg33Trp missense_variant 3/10 ENST00000453066.6 NP_000925.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SERPINF2ENST00000453066.6 linkuse as main transcriptc.97C>T p.Arg33Trp missense_variant 3/105 NM_000934.4 ENSP00000402286 P1P08697-1

Frequencies

GnomAD3 genomes
AF:
0.233
AC:
32634
AN:
139874
Hom.:
3589
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.227
Gnomad AMI
AF:
0.249
Gnomad AMR
AF:
0.277
Gnomad ASJ
AF:
0.192
Gnomad EAS
AF:
0.191
Gnomad SAS
AF:
0.403
Gnomad FIN
AF:
0.246
Gnomad MID
AF:
0.218
Gnomad NFE
AF:
0.219
Gnomad OTH
AF:
0.232
GnomAD3 exomes
AF:
0.242
AC:
43840
AN:
180824
Hom.:
5678
AF XY:
0.251
AC XY:
24277
AN XY:
96872
show subpopulations
Gnomad AFR exome
AF:
0.211
Gnomad AMR exome
AF:
0.274
Gnomad ASJ exome
AF:
0.194
Gnomad EAS exome
AF:
0.177
Gnomad SAS exome
AF:
0.382
Gnomad FIN exome
AF:
0.213
Gnomad NFE exome
AF:
0.213
Gnomad OTH exome
AF:
0.227
GnomAD4 exome
AF:
0.228
AC:
321824
AN:
1413266
Hom.:
38125
Cov.:
62
AF XY:
0.232
AC XY:
162282
AN XY:
699172
show subpopulations
Gnomad4 AFR exome
AF:
0.210
Gnomad4 AMR exome
AF:
0.271
Gnomad4 ASJ exome
AF:
0.197
Gnomad4 EAS exome
AF:
0.174
Gnomad4 SAS exome
AF:
0.382
Gnomad4 FIN exome
AF:
0.214
Gnomad4 NFE exome
AF:
0.218
Gnomad4 OTH exome
AF:
0.233
GnomAD4 genome
AF:
0.233
AC:
32651
AN:
139954
Hom.:
3590
Cov.:
26
AF XY:
0.241
AC XY:
16267
AN XY:
67612
show subpopulations
Gnomad4 AFR
AF:
0.227
Gnomad4 AMR
AF:
0.277
Gnomad4 ASJ
AF:
0.192
Gnomad4 EAS
AF:
0.191
Gnomad4 SAS
AF:
0.402
Gnomad4 FIN
AF:
0.246
Gnomad4 NFE
AF:
0.219
Gnomad4 OTH
AF:
0.236
Alfa
AF:
0.210
Hom.:
5724
Bravo
AF:
0.214
TwinsUK
AF:
0.223
AC:
827
ALSPAC
AF:
0.214
AC:
825
ESP6500AA
AF:
0.205
AC:
894
ESP6500EA
AF:
0.200
AC:
1705
ExAC
AF:
0.197
AC:
22950
Asia WGS
AF:
0.327
AC:
1135
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
17
DANN
Benign
0.89
DEOGEN2
Benign
0.20
.;T;.;.;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.48
T;T;T;T;.
MetaRNN
Benign
0.0041
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.55
.;N;N;.;N
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.14
N;N;N;N;N
REVEL
Uncertain
0.37
Sift
Benign
0.16
T;T;D;T;T
Sift4G
Benign
0.069
T;T;T;T;T
Polyphen
0.95
.;P;.;.;P
Vest4
0.045, 0.12, 0.051
MPC
0.47
ClinPred
0.013
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.068
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs2070863; hg19: chr17-1648502; COSMIC: COSV60664329; API