rs2236705

Positions:

• chr21-42312718-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFF3	NM_003226.4	c.230-449G>T		intron_variant		ENST00000518498.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFF3	ENST00000518498.3	c.230-449G>T		intron_variant		1	NM_003226.4	P1
TFF3	ENST00000398431.2	c.236-449G>T		intron_variant		3
TFF3	ENST00000489676.1	n.203-449G>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.145

Alfa AF: 0.152 Hom.: 2675

Bravo AF: 0.116

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.52
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236705; hg19: chr21-43732828; COSMIC: COSV52294874;