1-117093283-C-T

Variant names:

• chr1-117093283-C-T
• rs10494197
• NM_003594.4:c.2976+382C>T

Variant summary

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

The NM_003594.4(TTF2):​c.2976+382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 152,214 control chromosomes in the GnomAD database, including 528 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 0.062 (528 hom., cov: 32)
• Consequence: TTF2 NM_003594.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 5 publications found

Genes affected

TTF2 (HGNC:12398): (transcription termination factor 2) This gene encodes a member of the SWI2/SNF2 family of proteins, which play a critical role in altering protein-DNA interactions. The encoded protein has been shown to have dsDNA-dependent ATPase activity and RNA polymerase II termination activity. This protein interacts with cell division cycle 5-like, associates with human splicing complexes, and plays a role in pre-mRNA splicing. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTF2	NM_003594.4	c.2976+382C>T		intron_variant	Intron 18 of 22	ENST00000369466.9	NP_003585.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTF2	ENST00000369466.9	c.2976+382C>T		intron_variant	Intron 18 of 22	1	NM_003594.4	ENSP00000358478.3
TTF2	ENST00000492682.5	n.115+382C>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9404 AN: 152096 Hom.: 523 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0620 AC: 9433 AN: 152214 Hom.: 528 Cov.: 32 AF XY: 0.0626 AC XY: 4662 AN XY: 74426

African (AFR) AF: 0.132 AC: 5494 AN: 41496

American (AMR) AF: 0.0612 AC: 936 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3464

East Asian (EAS) AF: 0.109 AC: 563 AN: 5182

South Asian (SAS) AF: 0.115 AC: 556 AN: 4826

European-Finnish (FIN) AF: 0.0302 AC: 320 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0194 AC: 1320 AN: 68018

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0336 Hom.: 488

Bravo AF: 0.0645

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.64
PhyloP100		-0.18
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: rs10494197; hg19: chr1-117635905;