Genetic Variant TFF3:c.230-46G>A (chr21-42312315-C-T) – 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.230-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,551,714 control chromosomes in the GnomAD database, including 116,762 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 0.30 ( 8239 hom., cov: 32)

Exomes 𝑓: 0.38 ( 108523 hom. )

Consequence

TFF3
NM_003226.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.150

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 (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFF3	NM_003226.4 link	c.230-46G>A		intron_variant	Intron 2 of 2	ENST00000518498.3	NP_003217.4	Q07654

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TFF3	ENST00000518498.3 link	c.230-46G>A	intron_variant	Intron 2 of 2	1	NM_003226.4	ENSP00000430690.2	Q07654
TFF3	ENST00000398431.2 link	c.235-46G>A	intron_variant	Intron 2 of 2	3		ENSP00000381462.2	H7BYT0
TFF3	ENST00000489676.1 link	n.203-46G>A	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45277

AN:

151978

Hom.:

8242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.0499

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.323

GnomAD2 exomes

AF:

0.321

AC:

63020

AN:

196122

AF XY:

0.331

show subpopulations

Gnomad AFR exome

AF:

0.0967

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.0521

Gnomad FIN exome

AF:

0.356

Gnomad NFE exome

AF:

0.407

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.384

AC:

537732

AN:

1399618

Hom.:

108523

Cov.:

AF XY:

0.383

AC XY:

264468

AN XY:

689762

show subpopulations

African (AFR)

AF:

0.0883

AC:

2806

AN:

31784

American (AMR)

AF:

0.304

AC:

11482

AN:

37756

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

8882

AN:

21928

East Asian (EAS)

AF:

0.0450

AC:

1765

AN:

39262

South Asian (SAS)

AF:

0.327

AC:

24687

AN:

75386

European-Finnish (FIN)

AF:

0.355

AC:

17541

AN:

49480

Middle Eastern (MID)

AF:

0.347

AC:

1613

AN:

4646

European-Non Finnish (NFE)

AF:

0.415

AC:

448436

AN:

1081588

Other (OTH)

AF:

0.355

AC:

20520

AN:

57788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

15544

31088

46631

62175

77719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13826

27652

41478

55304

69130

<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:

0.298

AC:

45277

AN:

152096

Hom.:

8239

Cov.:

AF XY:

0.294

AC XY:

21868

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.104

AC:

4306

AN:

41526

American (AMR)

AF:

0.331

AC:

5050

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1406

AN:

3468

East Asian (EAS)

AF:

0.0502

AC:

259

AN:

5160

South Asian (SAS)

AF:

0.330

AC:

1590

AN:

4822

European-Finnish (FIN)

AF:

0.351

AC:

3718

AN:

10588

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27684

AN:

67940

Other (OTH)

AF:

0.319

AC:

674

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1520

3041

4561

6082

7602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.355

Hom.:

2350

Bravo

AF:

0.287

Asia WGS

AF:

0.174

AC:

606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

(source)

DANN

Benign

0.86

PhyloP100

-0.15

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

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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