rs225360

Variant names:

• chr21-42313821-G-A
• rs225360
• NM_003226.4:c.83-190C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003226.4(TFF3):​c.83-190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 611,458 control chromosomes in the GnomAD database, including 56,884 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 0.41 (13405 hom., cov: 32)
  • Exomes 𝑓: 0.43 (43479 hom.)
• Consequence: TFF3 NM_003226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFF3	NM_003226.4	c.83-190C>T		intron_variant	Intron 1 of 2	ENST00000518498.3	NP_003217.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFF3	ENST00000518498.3	c.83-190C>T		intron_variant	Intron 1 of 2	1	NM_003226.4	ENSP00000430690.2
TFF3	ENST00000398431.2	c.44-146C>T		intron_variant	Intron 1 of 2	3		ENSP00000381462.2
TFF3	ENST00000489676.1	n.-135C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62993 AN: 151884 Hom.: 13395 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.426 AC: 195867 AN: 459456 Hom.: 43479 AF XY: 0.424 AC XY: 100876 AN XY: 237736

Gnomad4 AFR exome AF: 0.387 AC: 4027 AN: 10410

Gnomad4 AMR exome AF: 0.410 AC: 4409 AN: 10756

Gnomad4 ASJ exome AF: 0.436 AC: 5565 AN: 12754

Gnomad4 EAS exome AF: 0.213 AC: 5234 AN: 24552

Gnomad4 SAS exome AF: 0.378 AC: 14466 AN: 38230

Gnomad4 FIN exome AF: 0.384 AC: 10764 AN: 28034

Gnomad4 NFE exome AF: 0.455 AC: 139856 AN: 307094

Gnomad4 Remaining exome AF: 0.419 AC: 10752 AN: 25654

GnomAD4 genome AF: 0.415 AC: 63047 AN: 152002 Hom.: 13405 Cov.: 32 AF XY: 0.408 AC XY: 30311 AN XY: 74310

Gnomad4 AFR AF: 0.382 AC: 0.381762 AN: 0.381762

Gnomad4 AMR AF: 0.414 AC: 0.414465 AN: 0.414465

Gnomad4 ASJ AF: 0.440 AC: 0.4397 AN: 0.4397

Gnomad4 EAS AF: 0.178 AC: 0.178281 AN: 0.178281

Gnomad4 SAS AF: 0.377 AC: 0.376821 AN: 0.376821

Gnomad4 FIN AF: 0.372 AC: 0.371788 AN: 0.371788

Gnomad4 NFE AF: 0.459 AC: 0.459415 AN: 0.459415

Gnomad4 OTH AF: 0.406 AC: 0.405687 AN: 0.405687

Alfa AF: 0.452 Hom.: 3170

Bravo AF: 0.416

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs225360; hg19: chr21-43733931;