Variant rs4888444 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018975.4(TERF2IP):c.970A>G(p.Lys324Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 1,614,148 control chromosomes in the GnomAD database, including 1,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.030 ( 91 hom., cov: 33)

Exomes 𝑓: 0.042 ( 1469 hom. )

Consequence

TERF2IP
NM_018975.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.26

Variant links:

Genes affected

TERF2IP (HGNC:19246): (TERF2 interacting protein) Enables G-rich strand telomeric DNA binding activity and phosphatase binding activity. Involved in several processes, including positive regulation of NIK/NF-kappaB signaling; regulation of nucleobase-containing compound metabolic process; and regulation of protein modification process. Located in chromosome, telomeric region; cytosol; and nuclear body. Part of shelterin complex. [provided by Alliance of Genome Resources, Apr 2022]

TERF2IP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013928115).

BP6

Variant 16-75656381-A-G is Benign according to our data. Variant chr16-75656381-A-G is described in ClinVar as [Benign]. Clinvar id is 1697661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75656381-A-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERF2IP	NM_018975.4 link	c.970A>G	p.Lys324Glu	missense_variant	3/3	ENST00000300086.5	NP_061848.2	Q9NYB0
TERF2IP	NR_144545.2 link	n.1210A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERF2IP	ENST00000300086.5 link	c.970A>G	p.Lys324Glu	missense_variant	3/3	1	NM_018975.4	ENSP00000300086.4		Q9NYB0

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4539

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00801

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0686

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0466

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0442

Gnomad OTH

AF:

0.0291

GnomAD3 exomes

AF:

0.0342

AC:

8587

AN:

251282

Hom.:

182

AF XY:

0.0374

AC XY:

5084

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00695

Gnomad AMR exome

AF:

0.0194

Gnomad ASJ exome

AF:

0.0606

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0495

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.0450

Gnomad OTH exome

AF:

0.0412

GnomAD4 exome

AF:

0.0423

AC:

61790

AN:

1461850

Hom.:

1469

Cov.:

AF XY:

0.0428

AC XY:

31106

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00627

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0593

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0497

Gnomad4 FIN exome

AF:

0.0154

Gnomad4 NFE exome

AF:

0.0461

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.0298

AC:

4535

AN:

152298

Hom.:

Cov.:

AF XY:

0.0286

AC XY:

2129

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00799

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.0686

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0460

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.0442

Gnomad4 OTH

AF:

0.0288

Alfa

AF:

0.0421

Hom.:

317

Bravo

AF:

0.0286

TwinsUK

AF:

0.0467

AC:

173

ALSPAC

AF:

0.0459

AC:

177

ESP6500AA

AF:

0.00887

AC:

ESP6500EA

AF:

0.0464

AC:

399

ExAC

AF:

0.0351

AC:

4266

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0490

EpiControl

AF:

0.0502

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.050

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.090

REVEL

Benign

0.084

Sift

Benign

0.83

Sift4G

Benign

1.0

Polyphen

0.0080

Vest4

0.041

MPC

0.033

ClinPred

0.015

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.19

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