rs4271

Variant names:

• chr7-93885943-T-A
• rs4271
• NM_006528.4:c.*877A>T

Variant summary

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

The NM_006528.4(TFPI2):​c.*877A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,132 control chromosomes in the GnomAD database, including 477 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 (477 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TFPI2 NM_006528.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 6 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=-0.89).
• 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.*877A>T		3_prime_UTR	Exon 5 of 5	NP_006519.1	P48307-1
	TFPI2	NM_001271003.2		c.*877A>T		3_prime_UTR	Exon 5 of 5	NP_001257932.1	P48307-2
	TFPI2	NM_001271004.2		c.*948A>T		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.*877A>T		3_prime_UTR	Exon 5 of 5	ENSP00000222543.5	P48307-1
	TFPI2	ENST00000898459.1		c.*877A>T		3_prime_UTR	Exon 4 of 4	ENSP00000568518.1
	GNGT1	ENST00000926552.1		c.-55-563T>A		intron	N/A	ENSP00000596611.1

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9489 AN: 152014 Hom.: 471 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0589

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0626 AC: 9524 AN: 152132 Hom.: 477 Cov.: 32 AF XY: 0.0655 AC XY: 4869 AN XY: 74390

African (AFR) AF: 0.112 AC: 4661 AN: 41532

American (AMR) AF: 0.110 AC: 1682 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3464

East Asian (EAS) AF: 0.166 AC: 860 AN: 5180

South Asian (SAS) AF: 0.0860 AC: 415 AN: 4826

European-Finnish (FIN) AF: 0.0252 AC: 267 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0192 AC: 1305 AN: 67904

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.0391 Hom.: 24

Bravo AF: 0.0685

Asia WGS AF: 0.161 AC: 556 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		0.15
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: rs4271; hg19: chr7-93515255;