rs225334

Variant names:

• chr21-42346451-G-A
• rs225334
• NM_005423.5:c.*82C>T

Variant summary

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

The NM_005423.5(TFF2):​c.*82C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,526,808 control chromosomes in the GnomAD database, including 298,960 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 0.65 (33446 hom., cov: 33)
  • Exomes 𝑓: 0.62 (265514 hom.)
• Consequence: TFF2 NM_005423.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• Publications: 14 publications found

Genes affected

TFF2 (HGNC:11756): (trefoil factor 2) 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. The encoded protein inhibits gastric acid secretion. 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005423.5. 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
	TFF2	NM_005423.5	MANE Select	c.*82C>T		3_prime_UTR	Exon 4 of 4	NP_005414.1	Q03403

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF2	ENST00000291526.5	TSL:1 MANE Select	c.*82C>T		3_prime_UTR	Exon 4 of 4	ENSP00000291526.4	Q03403
	TFF2	ENST00000463771.5	TSL:5	n.475C>T		non_coding_transcript_exon	Exon 4 of 4
	TFF2	ENST00000475297.1	TSL:3	n.602C>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99320 AN: 152072 Hom.: 33403 Cov.: 33

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.617 AC: 847765 AN: 1374618 Hom.: 265514 Cov.: 21 AF XY: 0.615 AC XY: 423619 AN XY: 688736

African (AFR) AF: 0.796 AC: 24687 AN: 31012

American (AMR) AF: 0.560 AC: 24573 AN: 43914

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 16236 AN: 25542

East Asian (EAS) AF: 0.280 AC: 10942 AN: 39136

South Asian (SAS) AF: 0.562 AC: 47021 AN: 83650

European-Finnish (FIN) AF: 0.576 AC: 30687 AN: 53314

Middle Eastern (MID) AF: 0.668 AC: 3754 AN: 5618

European-Non Finnish (NFE) AF: 0.633 AC: 654610 AN: 1034898

Other (OTH) AF: 0.613 AC: 35255 AN: 57534

GnomAD4 genome AF: 0.653 AC: 99431 AN: 152190 Hom.: 33446 Cov.: 33 AF XY: 0.645 AC XY: 48004 AN XY: 74408

African (AFR) AF: 0.787 AC: 32651 AN: 41512

American (AMR) AF: 0.614 AC: 9396 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1454 AN: 5178

South Asian (SAS) AF: 0.551 AC: 2658 AN: 4824

European-Finnish (FIN) AF: 0.564 AC: 5975 AN: 10598

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42979 AN: 67998

Other (OTH) AF: 0.655 AC: 1384 AN: 2114

Alfa AF: 0.642 Hom.: 40024

Bravo AF: 0.661

Asia WGS AF: 0.438 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.088
DANN	Benign	0.65
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs225334; hg19: chr21-43766560; COSMIC: COSV52295655;