rs225361

Variant names:

• chr21-42314874-A-G
• rs225361
• NM_003226.4:c.82+419T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003226.4(TFF3):​c.82+419T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,080 control chromosomes in the GnomAD database, including 17,210 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 0.47 (17210 hom., cov: 33)
• Consequence: TFF3 NM_003226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 3 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003226.4. 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
	TFF3	NM_003226.4	MANE Select	c.82+419T>C		intron	N/A	NP_003217.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF3	ENST00000518498.3	TSL:1 MANE Select	c.82+419T>C		intron	N/A	ENSP00000430690.2
	TFF3	ENST00000398431.2	TSL:3	c.43+419T>C		intron	N/A	ENSP00000381462.2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71160 AN: 151962 Hom.: 17194 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.468 AC: 71222 AN: 152080 Hom.: 17210 Cov.: 33 AF XY: 0.460 AC XY: 34221 AN XY: 74330

African (AFR) AF: 0.566 AC: 23501 AN: 41490

American (AMR) AF: 0.438 AC: 6691 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5178

South Asian (SAS) AF: 0.378 AC: 1823 AN: 4824

European-Finnish (FIN) AF: 0.378 AC: 3989 AN: 10552

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31079 AN: 67962

Other (OTH) AF: 0.453 AC: 955 AN: 2110

Alfa AF: 0.459 Hom.: 10242

Bravo AF: 0.478

Asia WGS AF: 0.289 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.60
PhyloP100		-1.4
PromoterAI		0.046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs225361; hg19: chr21-43734984;