7-93890146-T-G

Variant names:

• chr7-93890146-T-G
• rs111975101
• NM_006528.4:c.262A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_006528.4(TFPI2):​c.262A>C​(p.Arg88Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,604,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: TFPI2 NM_006528.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00100
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-93890146-T-G is Benign according to our data. Variant chr7-93890146-T-G is described in ClinVar as Benign. ClinVar VariationId is 730262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.001 with no splicing effect.

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.262A>C	p.Arg88Arg	synonymous	Exon 2 of 5	NP_006519.1	P48307-1
	TFPI2	NM_001271003.2		c.229A>C	p.Arg77Arg	synonymous	Exon 2 of 5	NP_001257932.1	P48307-2
	TFPI2	NM_001271004.2		c.262A>C	p.Arg88Arg	synonymous	Exon 2 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.262A>C	p.Arg88Arg	synonymous	Exon 2 of 5	ENSP00000222543.5	P48307-1
	TFPI2	ENST00000650573.1		c.262A>C	p.Arg88Arg	synonymous	Exon 2 of 5	ENSP00000497131.1	A0A3B3IS67
	TFPI2	ENST00000898459.1		c.262A>C	p.Arg88Arg	synonymous	Exon 2 of 4	ENSP00000568518.1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000343 AC: 85 AN: 248094 AF XY: 0.000246

Gnomad AFR exome AF: 0.00481

Gnomad AMR exome AF: 0.000205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000163 AC: 237 AN: 1452354 Hom.: 0 Cov.: 31 AF XY: 0.000150 AC XY: 108 AN XY: 720720

African (AFR) AF: 0.00517 AC: 172 AN: 33294

American (AMR) AF: 0.000451 AC: 20 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39388

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.000697 AC: 4 AN: 5736

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1104882

Other (OTH) AF: 0.000535 AC: 32 AN: 59852

GnomAD4 genome AF: 0.00144 AC: 219 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.00152 AC XY: 113 AN XY: 74490

African (AFR) AF: 0.00488 AC: 203 AN: 41580

American (AMR) AF: 0.000849 AC: 13 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000837 Hom.: 0

Bravo AF: 0.00170

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.61
PhyloP100		-0.0010
PromoterAI		0.011	Neutral

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: rs111975101; hg19: chr7-93519458;