21-42366497-G-A

Position:

• chr21-42366497-G-A

Variant summary

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

The NM_003225.3(TFF1):​c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,608,450 control chromosomes in the GnomAD database, including 19,838 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 (1745 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18093 hom.)
• Consequence: TFF1 NM_003225.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

Genes affected

TFF1 (HGNC:11755): (trefoil factor 1) 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, which is expressed in the gastric mucosa, has also been studied because of its expression in human tumors. 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFF1	NM_003225.3	c.-2C>T		5_prime_UTR_variant	1/3	ENST00000291527.3	NP_003216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFF1	ENST00000291527.3	c.-2C>T		5_prime_UTR_variant	1/3	1	NM_003225.3	ENSP00000291527.2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20201 AN: 152002 Hom.: 1751 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.163 AC: 40172 AN: 246870 Hom.: 4153 AF XY: 0.163 AC XY: 21822 AN XY: 133836

Gnomad AFR exome AF: 0.0718

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.447

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.147 AC: 213733 AN: 1456330 Hom.: 18093 Cov.: 33 AF XY: 0.148 AC XY: 107161 AN XY: 724096

Gnomad4 AFR exome AF: 0.0700

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.133 AC: 20193 AN: 152120 Hom.: 1745 Cov.: 32 AF XY: 0.136 AC XY: 10135 AN XY: 74342

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.148

Alfa AF: 0.127 Hom.: 1719

Bravo AF: 0.130

Asia WGS AF: 0.268 AC: 930 AN: 3478

EpiCase AF: 0.131

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.0
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2156310; hg19: chr21-43786606; COSMIC: COSV52299243;