rs8176531

Positions:

• chr2-187478980-G-A
• chr2-187478980-G-T

Variant summary

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

The NM_006287.6(TFPI):​c.628+5144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,004 control chromosomes in the GnomAD database, including 2,175 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 0.14 (2175 hom., cov: 32)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPI	NM_006287.6	c.628+5144C>T		intron_variant		ENST00000233156.9	NP_006278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPI	ENST00000233156.9	c.628+5144C>T		intron_variant		1	NM_006287.6	ENSP00000233156.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21728 AN: 151886 Hom.: 2173 Cov.: 32

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.143 AC: 21727 AN: 152004 Hom.: 2175 Cov.: 32 AF XY: 0.148 AC XY: 11009 AN XY: 74282

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.133

Alfa AF: 0.123 Hom.: 354

Bravo AF: 0.125

Asia WGS AF: 0.213 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs8176531; hg19: chr2-188343707;