chr17-1746874-C-T

Position:

• chr17-1746874-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.368-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,112,456 control chromosomes in the GnomAD database, including 299,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (37893 hom., cov: 31)
  • Exomes 𝑓: 0.74 (261698 hom.)
• Consequence: SERPINF2 NM_000934.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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 (BayesDel_noAF=-0.87).
• BP6: Variant 17-1746874-C-T is Benign according to our data. Variant chr17-1746874-C-T is described in ClinVar as [Benign]. Clinvar id is 1237847.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF2	NM_000934.4	c.368-145C>T		intron_variant		ENST00000453066.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF2	ENST00000453066.6	c.368-145C>T		intron_variant		5	NM_000934.4	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107078 AN: 151830 Hom.: 37860 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.737 AC: 707601 AN: 960508 Hom.: 261698 AF XY: 0.738 AC XY: 350811 AN XY: 475618

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.685

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.858

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.727

GnomAD4 genome AF: 0.705 AC: 107160 AN: 151948 Hom.: 37893 Cov.: 31 AF XY: 0.706 AC XY: 52451 AN XY: 74262

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.695

Alfa AF: 0.712 Hom.: 4586

Bravo AF: 0.697

Asia WGS AF: 0.818 AC: 2843 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6502935; hg19: chr17-1650168; COSMIC: COSV60663846;