rs2236705

Variant names:

• chr21-42312718-C-A
• rs2236705
• NM_003226.4:c.230-449G>T

Variant summary

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

The NM_003226.4(TFF3):​c.230-449G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,186 control chromosomes in the GnomAD database, including 1,500 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 0.13 (1500 hom., cov: 32)
• Consequence: TFF3 NM_003226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 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.230-449G>T		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.230-449G>T		intron	N/A	ENSP00000430690.2
	TFF3	ENST00000398431.2	TSL:3	c.235-449G>T		intron	N/A	ENSP00000381462.2
	TFF3	ENST00000489676.1	TSL:2	n.203-449G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19543 AN: 152066 Hom.: 1502 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.128 AC: 19544 AN: 152186 Hom.: 1500 Cov.: 32 AF XY: 0.134 AC XY: 10005 AN XY: 74396

African (AFR) AF: 0.0448 AC: 1859 AN: 41540

American (AMR) AF: 0.130 AC: 1982 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3468

East Asian (EAS) AF: 0.179 AC: 927 AN: 5176

South Asian (SAS) AF: 0.152 AC: 733 AN: 4826

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10584

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10722 AN: 67982

Other (OTH) AF: 0.145 AC: 307 AN: 2114

Alfa AF: 0.148 Hom.: 3881

Bravo AF: 0.116

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.52
DANN	Benign	0.53
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2236705; hg19: chr21-43732828; COSMIC: COSV52294874;