rs11701143

Positions:

• chr21-42315419-T-C

Variant summary

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

The variant allele was found at a frequency of 0.0328 in 1,614,134 control chromosomes in the GnomAD database, including 1,227 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 0.052 (325 hom., cov: 32)
  • Exomes 𝑓: 0.031 (902 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

(HGNC:):

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.42315419T>C		intergenic_region
TFF3	NM_003226.4	c.-45A>G		upstream_gene_variant		ENST00000518498.3	NP_003217.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFF3	ENST00000518498.3	c.-45A>G		upstream_gene_variant		1	NM_003226.4	ENSP00000430690.2

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7865 AN: 152160 Hom.: 325 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0338

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0282 AC: 7101 AN: 251482 Hom.: 201 AF XY: 0.0258 AC XY: 3513 AN XY: 135918

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00924

Gnomad FIN exome AF: 0.0145

Gnomad NFE exome AF: 0.0312

Gnomad OTH exome AF: 0.0287

GnomAD4 exome AF: 0.0309 AC: 45106 AN: 1461856 Hom.: 902 Cov.: 31 AF XY: 0.0300 AC XY: 21835 AN XY: 727228

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0203

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00912

Gnomad4 FIN exome AF: 0.0152

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0325

GnomAD4 genome AF: 0.0517 AC: 7877 AN: 152278 Hom.: 325 Cov.: 32 AF XY: 0.0490 AC XY: 3650 AN XY: 74462

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00809

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0338

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0371 Hom.: 236

Bravo AF: 0.0556

Asia WGS AF: 0.0140 AC: 52 AN: 3478

EpiCase AF: 0.0312

EpiControl AF: 0.0316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.91

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: rs11701143; hg19: chr21-43735529;