7-93886765-C-T

Variant names:

• chr7-93886765-C-T
• rs4264
• NM_006528.4:c.*55G>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.*55G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,120,410 control chromosomes in the GnomAD database, including 1,754 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 0.063 (473 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1281 hom.)
• Consequence: TFPI2 NM_006528.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI2	NM_006528.4	MANE Select	c.*55G>A		3_prime_UTR	Exon 5 of 5	NP_006519.1	P48307-1
	TFPI2	NM_001271003.2		c.*55G>A		3_prime_UTR	Exon 5 of 5	NP_001257932.1	P48307-2
	TFPI2	NM_001271004.2		c.*126G>A		3_prime_UTR	Exon 5 of 5	NP_001257933.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI2	ENST00000222543.11	TSL:1 MANE Select	c.*55G>A		3_prime_UTR	Exon 5 of 5	ENSP00000222543.5	P48307-1
	TFPI2	ENST00000650573.1		c.*55G>A		3_prime_UTR	Exon 5 of 5	ENSP00000497131.1	A0A3B3IS67
	TFPI2	ENST00000898459.1		c.*55G>A		3_prime_UTR	Exon 4 of 4	ENSP00000568518.1

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9492 AN: 152040 Hom.: 467 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0592

GnomAD4 exome AF: 0.0325 AC: 31503 AN: 968252 Hom.: 1281 Cov.: 13 AF XY: 0.0331 AC XY: 16454 AN XY: 497802

African (AFR) AF: 0.109 AC: 2091 AN: 19168

American (AMR) AF: 0.107 AC: 2304 AN: 21530

Ashkenazi Jewish (ASJ) AF: 0.0474 AC: 987 AN: 20818

East Asian (EAS) AF: 0.205 AC: 6372 AN: 31102

South Asian (SAS) AF: 0.0703 AC: 4154 AN: 59068

European-Finnish (FIN) AF: 0.0261 AC: 1172 AN: 44988

Middle Eastern (MID) AF: 0.0393 AC: 181 AN: 4604

European-Non Finnish (NFE) AF: 0.0173 AC: 12551 AN: 723630

Other (OTH) AF: 0.0390 AC: 1691 AN: 43344

GnomAD4 genome AF: 0.0626 AC: 9527 AN: 152158 Hom.: 473 Cov.: 32 AF XY: 0.0654 AC XY: 4867 AN XY: 74392

African (AFR) AF: 0.112 AC: 4662 AN: 41526

American (AMR) AF: 0.110 AC: 1676 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3466

East Asian (EAS) AF: 0.166 AC: 864 AN: 5190

South Asian (SAS) AF: 0.0863 AC: 416 AN: 4820

European-Finnish (FIN) AF: 0.0252 AC: 267 AN: 10600

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0192 AC: 1307 AN: 67954

Other (OTH) AF: 0.0591 AC: 125 AN: 2116

Alfa AF: 0.0337 Hom.: 177

Bravo AF: 0.0686

Asia WGS AF: 0.163 AC: 565 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.49
PhyloP100		-0.12
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: rs4264; hg19: chr7-93516077;