Genetic Variant NM_003226.4:c.83-190C>T (chr21-42313821-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_003226.4(TFF3):c.83-190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 611,458 control chromosomes in the GnomAD database, including 56,884 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 0.41 ( 13405 hom., cov: 32)

Exomes 𝑓: 0.43 ( 43479 hom. )

Consequence

TFF3
NM_003226.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.940

Publications

2 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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFF3	NM_003226.4 link	c.83-190C>T		intron_variant	Intron 1 of 2	ENST00000518498.3	NP_003217.4	Q07654

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TFF3	ENST00000518498.3 link	c.83-190C>T	intron_variant	Intron 1 of 2	1	NM_003226.4	ENSP00000430690.2	Q07654
TFF3	ENST00000398431.2 link	c.44-146C>T	intron_variant	Intron 1 of 2	3		ENSP00000381462.2	H7BYT0
TFF3	ENST00000489676.1 link	n.-135C>T	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62993

AN:

151884

Hom.:

13395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.409

GnomAD4 exome

AF:

0.426

AC:

195867

AN:

459456

Hom.:

43479

AF XY:

0.424

AC XY:

100876

AN XY:

237736

show subpopulations

African (AFR)

AF:

0.387

AC:

4027

AN:

10410

American (AMR)

AF:

0.410

AC:

4409

AN:

10756

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

5565

AN:

12754

East Asian (EAS)

AF:

0.213

AC:

5234

AN:

24552

South Asian (SAS)

AF:

0.378

AC:

14466

AN:

38230

European-Finnish (FIN)

AF:

0.384

AC:

10764

AN:

28034

Middle Eastern (MID)

AF:

0.403

AC:

794

AN:

1972

European-Non Finnish (NFE)

AF:

0.455

AC:

139856

AN:

307094

Other (OTH)

AF:

0.419

AC:

10752

AN:

25654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5171

10343

15514

20686

25857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1598

3196

4794

6392

7990

<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:

0.415

AC:

63047

AN:

152002

Hom.:

13405

Cov.:

AF XY:

0.408

AC XY:

30311

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.382

AC:

15821

AN:

41442

American (AMR)

AF:

0.414

AC:

6338

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1524

AN:

3466

East Asian (EAS)

AF:

0.178

AC:

921

AN:

5166

South Asian (SAS)

AF:

0.377

AC:

1811

AN:

4806

European-Finnish (FIN)

AF:

0.372

AC:

3935

AN:

10584

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.459

AC:

31209

AN:

67932

Other (OTH)

AF:

0.406

AC:

856

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1846

3693

5539

7386

9232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.452

Hom.:

3170

Bravo

AF:

0.416

Asia WGS

AF:

0.259

AC:

902

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.4

(source)

DANN

Benign

0.71

PhyloP100

0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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