dbSNP rs11701143: TFF3:c.-45A>G (chr21-42315419-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003226.4(TFF3):c.-45A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,614,134 control chromosomes in the GnomAD database, including 1,227 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 0.052 ( 325 hom., cov: 32)

Exomes 𝑓: 0.031 ( 902 hom. )

Consequence

TFF3
NM_003226.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

10 publications found

Variant links:

Genes affected

TFF3 (HGNC:11757): (trefoil factor 3) Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. This gene is expressed in goblet cells of the intestines and colon. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21. [provided by RefSeq, Jul 2008]

TFF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.011).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFF3	NM_003226.4 link	c.-45A>G		upstream_gene_variant		ENST00000518498.3	NP_003217.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFF3	ENST00000518498.3 link	c.-45A>G		upstream_gene_variant		1	NM_003226.4	ENSP00000430690.2
TFF3	ENST00000398431.2 link	c.-84A>G		upstream_gene_variant		3		ENSP00000381462.2

Frequencies

GnomAD3 genomes

AF:

0.0517

AC:

7865

AN:

152160

Hom.:

325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00809

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0338

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0282

AC:

7101

AN:

251482

AF XY:

0.0258

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.0183

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.0312

Gnomad OTH exome

AF:

0.0287

GnomAD4 exome

AF:

0.0309

AC:

45106

AN:

1461856

Hom.:

902

Cov.:

AF XY:

0.0300

AC XY:

21835

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.118

AC:

3959

AN:

33478

American (AMR)

AF:

0.0204

AC:

912

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

530

AN:

26134

East Asian (EAS)

AF:

0.000176

AC:

AN:

39698

South Asian (SAS)

AF:

0.00912

AC:

787

AN:

86258

European-Finnish (FIN)

AF:

0.0152

AC:

813

AN:

53412

Middle Eastern (MID)

AF:

0.0210

AC:

121

AN:

5768

European-Non Finnish (NFE)

AF:

0.0324

AC:

36017

AN:

1111994

Other (OTH)

AF:

0.0325

AC:

1960

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

2670

5341

8011

10682

13352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1376

2752

4128

5504

6880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0517

AC:

7877

AN:

152278

Hom.:

325

Cov.:

AF XY:

0.0490

AC XY:

3650

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.114

AC:

4720

AN:

41546

American (AMR)

AF:

0.0333

AC:

509

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00809

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0127

AC:

135

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0338

AC:

2296

AN:

68014

Other (OTH)

AF:

0.0407

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

361

722

1084

1445

1806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0387

Hom.:

544

Bravo

AF:

0.0556

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0312

EpiControl

AF:

0.0316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

(source)

DANN

Benign

0.91

PhyloP100

-1.5

PromoterAI

0.062

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over