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
• Publications: 2 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF3	NM_003226.4	MANE Select	c.83-190C>T		intron	N/A	NP_003217.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF3	ENST00000518498.3	TSL:1 MANE Select	c.83-190C>T		intron	N/A	ENSP00000430690.2	Q07654
	TFF3	ENST00000398431.2	TSL:3	c.44-146C>T		intron	N/A	ENSP00000381462.2	H7BYT0
	TFF3	ENST00000891173.1		c.83-190C>T		intron	N/A	ENSP00000561232.1

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

African (AFR) AF: 0.387 AC: 4027 AN: 10410

American (AMR) AF: 0.410 AC: 4409 AN: 10756

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 5565 AN: 12754

East Asian (EAS) AF: 0.213 AC: 5234 AN: 24552

South Asian (SAS) AF: 0.378 AC: 14466 AN: 38230

European-Finnish (FIN) AF: 0.384 AC: 10764 AN: 28034

Middle Eastern (MID) AF: 0.403 AC: 794 AN: 1972

European-Non Finnish (NFE) AF: 0.455 AC: 139856 AN: 307094

Other (OTH) 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

African (AFR) AF: 0.382 AC: 15821 AN: 41442

American (AMR) AF: 0.414 AC: 6338 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1524 AN: 3466

East Asian (EAS) AF: 0.178 AC: 921 AN: 5166

South Asian (SAS) AF: 0.377 AC: 1811 AN: 4806

European-Finnish (FIN) AF: 0.372 AC: 3935 AN: 10584

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31209 AN: 67932

Other (OTH) AF: 0.406 AC: 856 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		0.94
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

Other links and lift over

dbSNP: rs225360; hg19: chr21-43733931;