16-75647858-C-A

Variant summary

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

The NM_018975.4(TERF2IP):c.-25C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,601,202 control chromosomes in the GnomAD database, including 1,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 163 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1453 hom. )

Consequence

TERF2IP
NM_018975.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

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:

KARS1 (HGNC:6215): (lysyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KARS1 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 (BayesDel_noAF=-0.73).

BP6

Variant 16-75647858-C-A is Benign according to our data. Variant chr16-75647858-C-A is described in ClinVar as [Benign]. Clinvar id is 1249847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75647858-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TERF2IP	NM_018975.4 linkuse as main transcript	c.-25C>A	5_prime_UTR_variant	1/3	ENST00000300086.5
TERF2IP	XM_047434216.1 linkuse as main transcript	c.-25C>A	5_prime_UTR_variant	1/2
TERF2IP	NR_144545.2 linkuse as main transcript	n.86C>A	non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
TERF2IP	ENST00000300086.5 linkuse as main transcript	c.-25C>A	5_prime_UTR_variant	1/3	1	NM_018975.4	P1
KARS1	ENST00000566560.5 linkuse as main transcript	n.176+610G>T	intron_variant, non_coding_transcript_variant		1
TERF2IP	ENST00000653858.1 linkuse as main transcript	c.-25C>A	5_prime_UTR_variant	1/4

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6578

AN:

152186

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.0495

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0395

AC:

9644

AN:

244046

Hom.:

237

AF XY:

0.0403

AC XY:

5322

AN XY:

132218

show subpopulations

Gnomad AFR exome

AF:

0.0561

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0389

Gnomad EAS exome

AF:

0.0128

Gnomad SAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0661

Gnomad NFE exome

AF:

0.0418

Gnomad OTH exome

AF:

0.0381

GnomAD4 exome

AF:

0.0419

AC:

60736

AN:

1448898

Hom.:

1453

Cov.:

AF XY:

0.0420

AC XY:

30199

AN XY:

718934

show subpopulations

Gnomad4 AFR exome

AF:

0.0558

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0416

Gnomad4 EAS exome

AF:

0.0127

Gnomad4 SAS exome

AF:

0.0481

Gnomad4 FIN exome

AF:

0.0682

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0432

AC:

6581

AN:

152304

Hom.:

163

Cov.:

AF XY:

0.0429

AC XY:

3191

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0523

Gnomad4 AMR

AF:

0.0216

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.0497

Gnomad4 FIN

AF:

0.0651

Gnomad4 NFE

AF:

0.0416

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0332

Hom.:

Bravo

AF:

0.0410

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

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

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

Cadd

Benign

0.54

Dann

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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