rs8074026

Positions:

• chr17-1753779-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000934.4(SERPINF2):​c.1064-343T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,164 control chromosomes in the GnomAD database, including 39,193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39193 hom., cov: 33)
• Consequence: SERPINF2 NM_000934.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINF2	NM_000934.4	c.1064-343T>C		intron_variant		ENST00000453066.6	NP_000925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF2	ENST00000453066.6	c.1064-343T>C		intron_variant		5	NM_000934.4	ENSP00000402286	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108893 AN: 152046 Hom.: 39153 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.705

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.716 AC: 108985 AN: 152164 Hom.: 39193 Cov.: 33 AF XY: 0.718 AC XY: 53381 AN XY: 74392

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.709

Alfa AF: 0.734 Hom.: 55327

Bravo AF: 0.708

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs8074026; hg19: chr17-1657073;