chr21-42314874-A-G

Position:

• chr21-42314874-A-G

Variant summary

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

The NM_003226.4(TFF3):​c.82+419T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,080 control chromosomes in the GnomAD database, including 17,210 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 0.47 (17210 hom., cov: 33)
• Consequence: TFF3 NM_003226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFF3	NM_003226.4	c.82+419T>C		intron_variant		ENST00000518498.3	NP_003217.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFF3	ENST00000518498.3	c.82+419T>C		intron_variant		1	NM_003226.4	ENSP00000430690	P1
TFF3	ENST00000398431.2	c.44+419T>C		intron_variant		3		ENSP00000381462

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71160 AN: 151962 Hom.: 17194 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.468 AC: 71222 AN: 152080 Hom.: 17210 Cov.: 33 AF XY: 0.460 AC XY: 34221 AN XY: 74330

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.453

Alfa AF: 0.467 Hom.: 6482

Bravo AF: 0.478

Asia WGS AF: 0.289 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.60

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: rs225361; hg19: chr21-43734984;