Genetic Variant TFF1:c.85+149C>G (chr21-42366262-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000291527.3(TFF1):c.85+149C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 556,456 control chromosomes in the GnomAD database, including 4,002 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 0.084 ( 825 hom., cov: 32)

Exomes 𝑓: 0.11 ( 3177 hom. )

Consequence

TFF1
ENST00000291527.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.48

Publications

3 publications found

Variant links:

Genes affected

TFF1 (HGNC:11755): (trefoil factor 1) 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, which is expressed in the gastric mucosa, has also been studied because of its expression in human tumors. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21. [provided by RefSeq, Jul 2008]

TFF1 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000291527.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF1	NM_003225.3	MANE Select	c.85+149C>G		intron	N/A	NP_003216.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF1	ENST00000291527.3	TSL:1 MANE Select	c.85+149C>G		intron	N/A	ENSP00000291527.2

Frequencies

GnomAD3 genomes

AF:

0.0837

AC:

12738

AN:

152108

Hom.:

828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0668

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0996

Gnomad OTH

AF:

0.0929

GnomAD4 exome

AF:

0.111

AC:

44903

AN:

404230

Hom.:

3177

AF XY:

0.114

AC XY:

23676

AN XY:

208366

show subpopulations

African (AFR)

AF:

0.0170

AC:

200

AN:

11798

American (AMR)

AF:

0.0503

AC:

781

AN:

15540

Ashkenazi Jewish (ASJ)

AF:

0.0971

AC:

1109

AN:

11424

East Asian (EAS)

AF:

0.245

AC:

6954

AN:

28344

South Asian (SAS)

AF:

0.182

AC:

4612

AN:

25372

European-Finnish (FIN)

AF:

0.110

AC:

2899

AN:

26420

Middle Eastern (MID)

AF:

0.0639

AC:

106

AN:

1658

European-Non Finnish (NFE)

AF:

0.0991

AC:

25880

AN:

261110

Other (OTH)

AF:

0.105

AC:

2362

AN:

22564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1851

3702

5552

7403

9254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.0836

AC:

12728

AN:

152226

Hom.:

825

Cov.:

AF XY:

0.0875

AC XY:

6513

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0203

AC:

843

AN:

41578

American (AMR)

AF:

0.0665

AC:

1016

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

324

AN:

3472

East Asian (EAS)

AF:

0.257

AC:

1325

AN:

5164

South Asian (SAS)

AF:

0.188

AC:

910

AN:

4828

European-Finnish (FIN)

AF:

0.114

AC:

1203

AN:

10596

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0996

AC:

6772

AN:

67992

Other (OTH)

AF:

0.0929

AC:

196

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

578

1156

1735

2313

2891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0798

Hom.:

Bravo

AF:

0.0752

Asia WGS

AF:

0.194

AC:

675

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.18

(source)

DANN

Benign

0.44

PhyloP100

-2.5

PromoterAI

0.034

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over