Variant 1-117060509-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003594.4(TTF2):c.83G>A(p.Ser28Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00158 in 1,614,096 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 14 hom., cov: 34)

Exomes 𝑓: 0.00084 ( 20 hom. )

Consequence

TTF2
NM_003594.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.33

Variant links:

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]

TTF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010529101).

BP6

Variant 1-117060509-G-A is Benign according to our data. Variant chr1-117060509-G-A is described in ClinVar as [Benign]. Clinvar id is 775591.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00862 (1313/152348) while in subpopulation AFR AF= 0.0301 (1253/41584). AF 95% confidence interval is 0.0287. There are 14 homozygotes in gnomad4. There are 615 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTF2	NM_003594.4 linkuse as main transcript	c.83G>A	p.Ser28Asn	missense_variant	2/23	ENST00000369466.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTF2	ENST00000369466.9 linkuse as main transcript	c.83G>A	p.Ser28Asn	missense_variant	2/23	1	NM_003594.4	P1	Q9UNY4-1
TTF2	ENST00000470935.1 linkuse as main transcript	n.68G>A		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.00860

AC:

1309

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00234

AC:

587

AN:

251370

Hom.:

AF XY:

0.00172

AC XY:

234

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000842

AC:

1231

AN:

1461748

Hom.:

Cov.:

AF XY:

0.000723

AC XY:

526

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0304

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00862

AC:

1313

AN:

152348

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

615

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0301

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00214

Hom.:

Bravo

AF:

0.00991

ESP6500AA

AF:

0.0275

AC:

121

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00297

AC:

360

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.095

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.77

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.98

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.3

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.59

MVP

0.82

MPC

0.71

ClinPred

0.055

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.71

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over