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GeneBe

17-1745728-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000934.4(SERPINF2):c.186C>T(p.Ala62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,613,594 control chromosomes in the GnomAD database, including 2,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.039 ( 179 hom., cov: 31)
Exomes 𝑓: 0.052 ( 2378 hom. )

Consequence

SERPINF2
NM_000934.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.289
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-1745728-C-T is Benign according to our data. Variant chr17-1745728-C-T is described in ClinVar as [Benign]. Clinvar id is 256835.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.289 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINF2NM_000934.4 linkuse as main transcriptc.186C>T p.Ala62= synonymous_variant 5/10 ENST00000453066.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINF2ENST00000453066.6 linkuse as main transcriptc.186C>T p.Ala62= synonymous_variant 5/105 NM_000934.4 P1P08697-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0389
AC:
5919
AN:
152072
Hom.:
179
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0105
Gnomad AMI
AF:
0.0208
Gnomad AMR
AF:
0.0346
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00311
Gnomad FIN
AF:
0.0476
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0634
Gnomad OTH
AF:
0.0378
GnomAD3 exomes
AF:
0.0389
AC:
9736
AN:
250460
Hom.:
272
AF XY:
0.0387
AC XY:
5245
AN XY:
135484
show subpopulations
Gnomad AFR exome
AF:
0.00974
Gnomad AMR exome
AF:
0.0221
Gnomad ASJ exome
AF:
0.00527
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00506
Gnomad FIN exome
AF:
0.0507
Gnomad NFE exome
AF:
0.0643
Gnomad OTH exome
AF:
0.0414
GnomAD4 exome
AF:
0.0521
AC:
76208
AN:
1461404
Hom.:
2378
Cov.:
34
AF XY:
0.0508
AC XY:
36965
AN XY:
726984
show subpopulations
Gnomad4 AFR exome
AF:
0.00675
Gnomad4 AMR exome
AF:
0.0250
Gnomad4 ASJ exome
AF:
0.00635
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00490
Gnomad4 FIN exome
AF:
0.0547
Gnomad4 NFE exome
AF:
0.0617
Gnomad4 OTH exome
AF:
0.0436
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0389
AC:
5920
AN:
152190
Hom.:
179
Cov.:
31
AF XY:
0.0359
AC XY:
2674
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.0105
Gnomad4 AMR
AF:
0.0346
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00311
Gnomad4 FIN
AF:
0.0476
Gnomad4 NFE
AF:
0.0634
Gnomad4 OTH
AF:
0.0374
Alfa
AF:
0.0493
Hom.:
107
Bravo
AF:
0.0368
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.0568
EpiControl
AF:
0.0596

ClinVar

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

Submissions by phenotype

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

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
3.6
Dann
Benign
0.40
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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: rs35259159; hg19: chr17-1649022; COSMIC: COSV60665245; API