7-93890088-C-T

Variant names:

• chr7-93890088-C-T
• rs59740167
• NM_006528.4:c.271+49G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006528.4. 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
	TFPI2	NM_006528.4	MANE Select	c.271+49G>A		intron	N/A	NP_006519.1
	TFPI2	NM_001271003.2		c.238+49G>A		intron	N/A	NP_001257932.1
	TFPI2	NM_001271004.2		c.271+49G>A		intron	N/A	NP_001257933.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI2	ENST00000222543.11	TSL:1 MANE Select	c.271+49G>A		intron	N/A	ENSP00000222543.5
	TFPI2	ENST00000461482.1	TSL:2	n.395G>A		non_coding_transcript_exon	Exon 2 of 2
	TFPI2	ENST00000650573.1		c.271+49G>A		intron	N/A	ENSP00000497131.1

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

GnomAD2 exomes AF: 0.0567 AC: 9880 AN: 174344 AF XY: 0.0526

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 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

African (AFR) AF: 0.107 AC: 3178 AN: 29716

American (AMR) AF: 0.107 AC: 3365 AN: 31414

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 977 AN: 20676

East Asian (EAS) AF: 0.200 AC: 7248 AN: 36200

South Asian (SAS) AF: 0.0743 AC: 5207 AN: 70122

European-Finnish (FIN) AF: 0.0269 AC: 1342 AN: 49936

Middle Eastern (MID) AF: 0.0358 AC: 188 AN: 5246

European-Non Finnish (NFE) AF: 0.0163 AC: 17175 AN: 1051726

Other (OTH) AF: 0.0392 AC: 2158 AN: 55108

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

African (AFR) AF: 0.109 AC: 4514 AN: 41556

American (AMR) AF: 0.107 AC: 1642 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3472

East Asian (EAS) AF: 0.168 AC: 869 AN: 5170

South Asian (SAS) AF: 0.0857 AC: 414 AN: 4832

European-Finnish (FIN) AF: 0.0256 AC: 272 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0188 AC: 1278 AN: 68040

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0389 Hom.: 43

Bravo AF: 0.0672

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.91
PhyloP100		-0.72
PromoterAI		0.011	Neutral
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: rs59740167; hg19: chr7-93519400;