rs59999573

Positions:

• chr7-93890078-C-T

Variant summary

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

The ENST00000222543.11(TFPI2):​c.271+59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 1,493,138 control chromosomes in the GnomAD database, including 3,019 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 0.076 (588 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2431 hom.)
• Consequence: TFPI2 ENST00000222543.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

Genes affected

TFPI2 (HGNC:11761): (tissue factor pathway inhibitor 2) This gene encodes a member of the Kunitz-type serine proteinase inhibitor family. The protein can inhibit a variety of serine proteases including factor VIIa/tissue factor, factor Xa, plasmin, trypsin, chymotryspin and plasma kallikrein. This gene has been identified as a tumor suppressor gene in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

GNGT1 (HGNC:4411): (G protein subunit gamma transducin 1) This gene encodes the gamma subunit of transducin, a guanine nucleotide-binding protein (G protein) that is found in rod outer segments. Transducin, also known as GMPase, mediates the activation of a cyclic GTP-specific (guanosine monophosphate) phosphodiesterase by rhodopsin. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPI2	NM_006528.4	c.271+59G>A		intron_variant		ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.238+59G>A		intron_variant			NP_001257932.1
TFPI2	NM_001271004.2	c.271+59G>A		intron_variant			NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11	c.271+59G>A		intron_variant		1	NM_006528.4	ENSP00000222543	P2

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11516 AN: 152170 Hom.: 581 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0673

GnomAD4 exome AF: 0.0501 AC: 67194 AN: 1340850 Hom.: 2431 Cov.: 26 AF XY: 0.0507 AC XY: 33241 AN XY: 655994

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.0486

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.0335

Gnomad4 NFE exome AF: 0.0391

Gnomad4 OTH exome AF: 0.0561

GnomAD4 genome AF: 0.0759 AC: 11555 AN: 152288 Hom.: 588 Cov.: 33 AF XY: 0.0771 AC XY: 5743 AN XY: 74454

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0388

Gnomad4 OTH AF: 0.0671

Alfa AF: 0.0485 Hom.: 47

Bravo AF: 0.0826

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.87

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: rs59999573; hg19: chr7-93519390;