11-46729851-T-C

Position:

• chr11-46729851-T-C

Variant summary

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

The NM_000506.5(F2):​c.1654+290T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,018 control chromosomes in the GnomAD database, including 2,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (2474 hom., cov: 31)
• Consequence: F2 NM_000506.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.285

Genes affected

F2 (HGNC:3535): (coagulation factor II, thrombin) This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-46729851-T-C is Benign according to our data. Variant chr11-46729851-T-C is described in ClinVar as [Benign]. Clinvar id is 1258693.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2	NM_000506.5	c.1654+290T>C		intron_variant		ENST00000311907.10	NP_000497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2	ENST00000311907.10	c.1654+290T>C		intron_variant		1	NM_000506.5	ENSP00000308541.5
F2	ENST00000530231.5	c.1537+290T>C		intron_variant		5		ENSP00000433907.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21475 AN: 151900 Hom.: 2462 Cov.: 31

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.141 AC: 21490 AN: 152018 Hom.: 2474 Cov.: 31 AF XY: 0.151 AC XY: 11252 AN XY: 74296

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.0796

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.122

Alfa AF: 0.128 Hom.: 241

Bravo AF: 0.140

Asia WGS AF: 0.312 AC: 1084 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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.54

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: rs2282687; hg19: chr11-46751401;