7-93886681-T-G

Variant names:

• chr7-93886681-T-G
• rs4517
• NM_006528.4:c.*139A>C

Variant summary

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

The NM_006528.4(TFPI2):​c.*139A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 607,298 control chromosomes in the GnomAD database, including 27,254 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 0.26 (5883 hom., cov: 32)
  • Exomes 𝑓: 0.29 (21371 hom.)
• Consequence: TFPI2 NM_006528.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 9 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPI2	NM_006528.4	c.*139A>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.*139A>C		3_prime_UTR_variant	Exon 5 of 5		NP_001257932.1
TFPI2	NM_001271004.2	c.*210A>C		3_prime_UTR_variant	Exon 5 of 5		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11	c.*139A>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_006528.4	ENSP00000222543.5
TFPI2	ENST00000650573.1	c.*139A>C		3_prime_UTR_variant	Exon 5 of 5			ENSP00000497131.1
TFPI2	ENST00000451238.1	c.*210A>C		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000416370.1
GNGT1	ENST00000455502.5	c.-12+132T>G		intron_variant	Intron 2 of 3	2		ENSP00000395857.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39214 AN: 151822 Hom.: 5882 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.292 AC: 133048 AN: 455358 Hom.: 21371 Cov.: 6 AF XY: 0.296 AC XY: 71207 AN XY: 240706

African (AFR) AF: 0.153 AC: 1432 AN: 9360

American (AMR) AF: 0.428 AC: 4473 AN: 10456

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 3063 AN: 14538

East Asian (EAS) AF: 0.585 AC: 14314 AN: 24456

South Asian (SAS) AF: 0.397 AC: 14242 AN: 35908

European-Finnish (FIN) AF: 0.334 AC: 10232 AN: 30592

Middle Eastern (MID) AF: 0.281 AC: 555 AN: 1974

European-Non Finnish (NFE) AF: 0.256 AC: 77541 AN: 303174

Other (OTH) AF: 0.289 AC: 7196 AN: 24900

GnomAD4 genome AF: 0.258 AC: 39243 AN: 151940 Hom.: 5883 Cov.: 32 AF XY: 0.269 AC XY: 19940 AN XY: 74256

African (AFR) AF: 0.152 AC: 6298 AN: 41500

American (AMR) AF: 0.368 AC: 5616 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 706 AN: 3462

East Asian (EAS) AF: 0.617 AC: 3185 AN: 5164

South Asian (SAS) AF: 0.394 AC: 1902 AN: 4832

European-Finnish (FIN) AF: 0.332 AC: 3504 AN: 10546

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17170 AN: 67866

Other (OTH) AF: 0.281 AC: 591 AN: 2100

Alfa AF: 0.206 Hom.: 1165

Bravo AF: 0.259

Asia WGS AF: 0.477 AC: 1647 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.2
DANN	Benign	0.90
PhyloP100		0.031
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: rs4517; hg19: chr7-93515993;