chr2-187554863-G-A

Position:

• chr2-187554863-G-A

Variant summary

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

The ENST00000421427.5(TFPI):​c.-274-514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,934 control chromosomes in the GnomAD database, including 2,609 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 0.17 (2609 hom., cov: 32)
• Consequence: TFPI ENST00000421427.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

TFPI (HGNC:11760): (tissue factor pathway inhibitor) This gene encodes a Kunitz-type serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. The product of this gene inhibits the activated factor X and VIIa-TF proteases in an autoregulatory loop. Inhibition of the encoded protein restores hemostasis in animal models of hemophilia. This gene encodes multiple protein isoforms that differ in their inhibitory activity, specificity and cellular localization. [provided by RefSeq, Jul 2016]

(HGNC:):

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 = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.187554863G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPI	ENST00000421427.5	c.-274-514C>T		intron_variant		3		ENSP00000408170.1
CALCRL-AS1	ENST00000412276.6	n.829+470G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25977 AN: 151818 Hom.: 2608 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.171 AC: 25999 AN: 151934 Hom.: 2609 Cov.: 32 AF XY: 0.175 AC XY: 12964 AN XY: 74268

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.173

Alfa AF: 0.131 Hom.: 2221

Bravo AF: 0.181

Asia WGS AF: 0.257 AC: 894 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	0.61
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10153820; hg19: chr2-188419590;