rs7573488

Positions:

• chr2-187533353-G-C

Variant summary

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

The NM_006287.6(TFPI):​c.-3+20847C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,058 control chromosomes in the GnomAD database, including 4,494 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 0.24 (4494 hom., cov: 32)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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]

CALCRL-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPI	NM_006287.6	c.-3+20847C>G		intron_variant		ENST00000233156.9	NP_006278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPI	ENST00000233156.9	c.-3+20847C>G		intron_variant		1	NM_006287.6	ENSP00000233156.3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36409 AN: 151940 Hom.: 4487 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.240 AC: 36454 AN: 152058 Hom.: 4494 Cov.: 32 AF XY: 0.241 AC XY: 17876 AN XY: 74320

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.242

Alfa AF: 0.258 Hom.: 674

Bravo AF: 0.231

Asia WGS AF: 0.248 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7573488; hg19: chr2-188398080;