rs2268300

Variant names:

• chr2-187470008-A-G
• rs2268300
• NM_006287.6:c.629-2076T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006287.6(TFPI):​c.629-2076T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 152,226 control chromosomes in the GnomAD database, including 215 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 0.023 (215 hom., cov: 32)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006287.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI	NM_006287.6	MANE Select	c.629-2076T>C		intron	N/A	NP_006278.1
	TFPI	NM_001329239.2		c.629-2076T>C		intron	N/A	NP_001316168.1
	TFPI	NM_001329240.2		c.629-2076T>C		intron	N/A	NP_001316169.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI	ENST00000233156.9	TSL:1 MANE Select	c.629-2076T>C		intron	N/A	ENSP00000233156.3
	TFPI	ENST00000392365.5	TSL:5	c.629-2076T>C		intron	N/A	ENSP00000376172.1
	TFPI	ENST00000435414.5	TSL:5	c.590-2076T>C		intron	N/A	ENSP00000409177.1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3459 AN: 152108 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0227 AC: 3454 AN: 152226 Hom.: 215 Cov.: 32 AF XY: 0.0272 AC XY: 2027 AN XY: 74422

African (AFR) AF: 0.00248 AC: 103 AN: 41570

American (AMR) AF: 0.104 AC: 1584 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3464

East Asian (EAS) AF: 0.188 AC: 973 AN: 5166

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4826

European-Finnish (FIN) AF: 0.0423 AC: 449 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 68008

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0187 Hom.: 73

Bravo AF: 0.0298

Asia WGS AF: 0.0800 AC: 279 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.85
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2268300; hg19: chr2-188334735;