chr17-1753779-T-C

Variant names:

• chr17-1753779-T-C
• rs8074026
• NM_000934.4:c.1064-343T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

SERPINF2 Gene-Disease associations (from GenCC):

• alpha-2-plasmin inhibitor deficiency

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000934.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF2	NM_000934.4	MANE Select	c.1064-343T>C		intron	N/A	NP_000925.2
	SERPINF2	NM_001165920.1		c.1064-343T>C		intron	N/A	NP_001159392.1
	SERPINF2	NM_001165921.2		c.872-343T>C		intron	N/A	NP_001159393.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF2	ENST00000453066.6	TSL:5 MANE Select	c.1064-343T>C		intron	N/A	ENSP00000402286.2
	SERPINF2	ENST00000382061.5	TSL:1	c.1064-343T>C		intron	N/A	ENSP00000371493.4
	SERPINF2	ENST00000324015.7	TSL:5	c.1064-343T>C		intron	N/A	ENSP00000321853.3

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

African (AFR) AF: 0.638 AC: 26493 AN: 41510

American (AMR) AF: 0.697 AC: 10650 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4490 AN: 5184

South Asian (SAS) AF: 0.761 AC: 3669 AN: 4824

European-Finnish (FIN) AF: 0.749 AC: 7924 AN: 10580

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50900 AN: 68004

Other (OTH) AF: 0.709 AC: 1495 AN: 2110

Alfa AF: 0.731 Hom.: 68981

Bravo AF: 0.708

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.60
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8074026; hg19: chr17-1657073;