9-132382316-C-T

Variant names:

• chr9-132382316-C-T
• rs11243755
• NM_007344.4:c.2379-3172G>A

Variant summary

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

The NM_007344.4(TTF1):​c.2379-3172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,166 control chromosomes in the GnomAD database, including 3,023 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 0.20 (3023 hom., cov: 32)
• Consequence: TTF1 NM_007344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 3 publications found

Genes affected

TTF1 (HGNC:12397): (transcription termination factor 1) This gene encodes a transcription termination factor that is localized to the nucleolus and plays a critical role in ribosomal gene transcription. The encoded protein mediates the termination of RNA polymerase I transcription by binding to Sal box terminator elements downstream of pre-rRNA coding regions. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. This gene shares the symbol/alias 'TFF1' with another gene, NK2 homeobox 1, also known as thyroid transcription factor 1, which plays a role in the regulation of thyroid-specific gene expression. [provided by RefSeq, Apr 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTF1	NM_007344.4	c.2379-3172G>A		intron_variant	Intron 9 of 10	ENST00000334270.3	NP_031370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTF1	ENST00000334270.3	c.2379-3172G>A		intron_variant	Intron 9 of 10	1	NM_007344.4	ENSP00000333920.2
TTF1	ENST00000612514.4	c.834-3172G>A		intron_variant	Intron 8 of 9	1		ENSP00000481441.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29685 AN: 152048 Hom.: 3024 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.195 AC: 29696 AN: 152166 Hom.: 3023 Cov.: 32 AF XY: 0.195 AC XY: 14524 AN XY: 74400

African (AFR) AF: 0.212 AC: 8783 AN: 41496

American (AMR) AF: 0.192 AC: 2940 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1712 AN: 5178

South Asian (SAS) AF: 0.169 AC: 815 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1734 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12435 AN: 67998

Other (OTH) AF: 0.196 AC: 413 AN: 2110

Alfa AF: 0.189 Hom.: 11442

Bravo AF: 0.199

Asia WGS AF: 0.237 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		0.56
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: rs11243755; hg19: chr9-135257703; COSMIC: COSV57503004; COSMIC: COSV57503004;