rs59740167

chr7-93890088-C-T

Variant summary

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

The NM_006528.4(TFPI2):c.271+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,502,460 control chromosomes in the GnomAD database, including 2,046 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 0.061 (447 hom., cov: 33)
  • Exomes 𝑓: 0.030 (1599 hom.)
• Consequence: TFPI2 NM_006528.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPI2	NM_006528.4	c.271+49G>A		intron_variant		ENST00000222543.11
TFPI2	NM_001271003.2	c.238+49G>A		intron_variant
TFPI2	NM_001271004.2	c.271+49G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI2	ENST00000222543.11	c.271+49G>A		intron_variant		1	NM_006528.4	P2

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9293 AN: 152198 Hom.: 442 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0583

GnomAD3 exomes AF: 0.0567 AC: 9880 AN: 174344 Hom.: 470 AF XY: 0.0526 AC XY: 4952 AN XY: 94060

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.0443

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.0750

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0447

GnomAD4 exome AF: 0.0302 AC: 40838 AN: 1350144 Hom.: 1599 Cov.: 29 AF XY: 0.0310 AC XY: 20473 AN XY: 661074

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0473

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.0743

Gnomad4 FIN exome AF: 0.0269

Gnomad4 NFE exome AF: 0.0163

Gnomad4 OTH exome AF: 0.0392

GnomAD4 genome AF: 0.0612 AC: 9322 AN: 152316 Hom.: 447 Cov.: 33 AF XY: 0.0637 AC XY: 4742 AN XY: 74468

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0857

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0188

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0367 Hom.: 37

Bravo AF: 0.0672

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.6
Dann	Benign	0.91

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: rs59740167; hg19: chr7-93519400;