rs13051704

Positions:

• chr21-42366262-G-C

Variant summary

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

The NM_003225.3(TFF1):​c.85+149C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 556,456 control chromosomes in the GnomAD database, including 4,002 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 0.084 (825 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3177 hom.)
• Consequence: TFF1 NM_003225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFF1	NM_003225.3	c.85+149C>G		intron_variant		ENST00000291527.3	NP_003216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFF1	ENST00000291527.3	c.85+149C>G		intron_variant		1	NM_003225.3	ENSP00000291527	P1

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12738 AN: 152108 Hom.: 828 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0929

GnomAD4 exome AF: 0.111 AC: 44903 AN: 404230 Hom.: 3177 AF XY: 0.114 AC XY: 23676 AN XY: 208366

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.0503

Gnomad4 ASJ exome AF: 0.0971

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0991

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0836 AC: 12728 AN: 152226 Hom.: 825 Cov.: 32 AF XY: 0.0875 AC XY: 6513 AN XY: 74436

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0996

Gnomad4 OTH AF: 0.0929

Alfa AF: 0.0798 Hom.: 85

Bravo AF: 0.0752

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.44

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: rs13051704; hg19: chr21-43786371;