dbSNP rs225334: TFF2:c.*82C>T (chr21-42346451-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005423.5(TFF2):c.*82C>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 0.62 in 1,526,808 control chromosomes in the GnomAD database, including 298,960 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 0.65 ( 33446 hom., cov: 33)

Exomes 𝑓: 0.62 ( 265514 hom. )

Consequence

TFF2
NM_005423.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.991

Publications

14 publications found

Variant links:

Genes affected

TFF2 (HGNC:11756): (trefoil factor 2) 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. The encoded protein inhibits gastric acid secretion. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21. [provided by RefSeq, Jul 2008]

TFF2 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFF2	NM_005423.5 link	c.*82C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000291526.5	NP_005414.1	Q03403

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TFF2	ENST00000291526.5 link	c.*82C>T	3_prime_UTR_variant	Exon 4 of 4	1	NM_005423.5	ENSP00000291526.4	Q03403
TFF2	ENST00000463771.5 link	n.475C>T	non_coding_transcript_exon_variant	Exon 4 of 4	5
TFF2	ENST00000475297.1 link	n.602C>T	non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

99320

AN:

152072

Hom.:

33403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.564

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.652

GnomAD4 exome

AF:

0.617

AC:

847765

AN:

1374618

Hom.:

265514

Cov.:

AF XY:

0.615

AC XY:

423619

AN XY:

688736

show subpopulations

African (AFR)

AF:

0.796

AC:

24687

AN:

31012

American (AMR)

AF:

0.560

AC:

24573

AN:

43914

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

16236

AN:

25542

East Asian (EAS)

AF:

0.280

AC:

10942

AN:

39136

South Asian (SAS)

AF:

0.562

AC:

47021

AN:

83650

European-Finnish (FIN)

AF:

0.576

AC:

30687

AN:

53314

Middle Eastern (MID)

AF:

0.668

AC:

3754

AN:

5618

European-Non Finnish (NFE)

AF:

0.633

AC:

654610

AN:

1034898

Other (OTH)

AF:

0.613

AC:

35255

AN:

57534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

15252

30505

45757

61010

76262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16812

33624

50436

67248

84060

<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:

0.653

AC:

99431

AN:

152190

Hom.:

33446

Cov.:

AF XY:

0.645

AC XY:

48004

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.787

AC:

32651

AN:

41512

American (AMR)

AF:

0.614

AC:

9396

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

2216

AN:

3468

East Asian (EAS)

AF:

0.281

AC:

1454

AN:

5178

South Asian (SAS)

AF:

0.551

AC:

2658

AN:

4824

European-Finnish (FIN)

AF:

0.564

AC:

5975

AN:

10598

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.632

AC:

42979

AN:

67998

Other (OTH)

AF:

0.655

AC:

1384

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1703

3406

5108

6811

8514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.642

Hom.:

40024

Bravo

AF:

0.661

Asia WGS

AF:

0.438

AC:

1526

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.088

(source)

DANN

Benign

0.65

PhyloP100

-0.99

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