1-117093283-C-T

Position:

• chr1-117093283-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TTF2	NM_003594.4	c.2976+382C>T		intron_variant		ENST00000369466.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTF2	ENST00000369466.9	c.2976+382C>T		intron_variant		1	NM_003594.4	P1
TTF2	ENST00000492682.5	n.115+382C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0235 Hom.: 78

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10494197; hg19: chr1-117635905;