chr17-1754605-G-A

Variant names:

• chr17-1754605-G-A
• rs1057355
• NM_000934.4:c.*71G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000934.4(SERPINF2):​c.*71G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,404,718 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: SERPINF2 NM_000934.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 15 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF2	NM_000934.4	c.*71G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000453066.6	NP_000925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF2	ENST00000453066.6	c.*71G>A		3_prime_UTR_variant	Exon 10 of 10	5	NM_000934.4	ENSP00000402286.2
SERPINF2	ENST00000382061.5	c.*71G>A		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000371493.4
SERPINF2	ENST00000324015.7	c.*71G>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000321853.3
SERPINF2	ENST00000450523.6	c.*71G>A		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000403877.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000356 AC: 5 AN: 1404718 Hom.: 0 Cov.: 29 AF XY: 0.00000573 AC XY: 4 AN XY: 697806

African (AFR) AF: 0.00 AC: 0 AN: 31896

American (AMR) AF: 0.0000800 AC: 3 AN: 37494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23410

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 79894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091332

Other (OTH) AF: 0.00 AC: 0 AN: 58472

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 21632

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.88
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1057355; hg19: chr17-1657899;