17-1745208-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.790

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
SERPINF2	NM_000934.4	c.97C>T	p.Arg33Trp	missense_variant	3/10	ENST00000453066.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF2	ENST00000453066.6	c.97C>T	p.Arg33Trp	missense_variant	3/10	5	NM_000934.4	P1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 32634 AN: 139874 Hom.: 3589 Cov.: 26

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

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

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

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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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
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
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

Other links and lift over

dbSNP: rs2070863; hg19: chr17-1648502; COSMIC: COSV60664329;