chr2-187471370-T-G

Position:

• chr2-187471370-T-G

Variant summary

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

The NM_006287.6(TFPI):​c.629-3438A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,926 control chromosomes in the GnomAD database, including 8,645 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 0.33 (8645 hom., cov: 32)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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:55863): (CALCRL and TFPI antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPI	NM_006287.6	c.629-3438A>C		intron_variant		ENST00000233156.9	NP_006278.1
CALCRL-AS1	XR_007087504.1	n.3420-28136T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPI	ENST00000233156.9	c.629-3438A>C		intron_variant		1	NM_006287.6	ENSP00000233156	P1
CALCRL-AS1	ENST00000412276.6	n.190-28136T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50108 AN: 151808 Hom.: 8637 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.330 AC: 50147 AN: 151926 Hom.: 8645 Cov.: 32 AF XY: 0.326 AC XY: 24194 AN XY: 74260

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.347

Alfa AF: 0.338 Hom.: 1145

Bravo AF: 0.330

Asia WGS AF: 0.257 AC: 886 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.73

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: rs3771059; hg19: chr2-188336097;