rs533093

Positions:

• chr21-42312315-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003226.4(TFF3):​c.230-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,551,714 control chromosomes in the GnomAD database, including 116,762 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 0.30 (8239 hom., cov: 32)
  • Exomes 𝑓: 0.38 (108523 hom.)
• Consequence: TFF3 NM_003226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFF3	NM_003226.4	c.230-46G>A		intron_variant		ENST00000518498.3	NP_003217.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFF3	ENST00000518498.3	c.230-46G>A		intron_variant		1	NM_003226.4	ENSP00000430690.2
TFF3	ENST00000398431.2	c.235-46G>A		intron_variant		3		ENSP00000381462.2
TFF3	ENST00000489676.1	n.203-46G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45277 AN: 151978 Hom.: 8242 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.323

GnomAD3 exomes AF: 0.321 AC: 63020 AN: 196122 Hom.: 11494 AF XY: 0.331 AC XY: 34440 AN XY: 104010

Gnomad AFR exome AF: 0.0967

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.401

Gnomad EAS exome AF: 0.0521

Gnomad SAS exome AF: 0.324

Gnomad FIN exome AF: 0.356

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.384 AC: 537732 AN: 1399618 Hom.: 108523 Cov.: 34 AF XY: 0.383 AC XY: 264468 AN XY: 689762

Gnomad4 AFR exome AF: 0.0883

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.0450

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.415

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.298 AC: 45277 AN: 152096 Hom.: 8239 Cov.: 32 AF XY: 0.294 AC XY: 21868 AN XY: 74358

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.0502

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.319

Alfa AF: 0.355 Hom.: 2350

Bravo AF: 0.287

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs533093; hg19: chr21-43732425;