rs2233810

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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:3

Conservation

PhyloP100: -1.09

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 89
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
leukoencephalopathy, progressive, infantile-onset, with or without deafness
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease recessive intermediate B
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

KARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF2IP	NM_018975.4 link	c.-25C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000300086.5	NP_061848.2	Q9NYB0
KARS1	NM_005548.3 link	c.-219G>T		upstream_gene_variant		ENST00000302445.8	NP_005539.1	Q15046-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF2IP	ENST00000300086.5 link	c.-25C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_018975.4	ENSP00000300086.4		Q9NYB0
KARS1	ENST00000302445.8 link	c.-219G>T		upstream_gene_variant		1	NM_005548.3	ENSP00000303043.3		Q15046-1

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

GnomAD2 exomes

AF:

0.0395

AC:

9644

AN:

244046

AF XY:

0.0403

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 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

African (AFR)

AF:

0.0558

AC:

1847

AN:

33126

American (AMR)

AF:

0.0154

AC:

671

AN:

43654

Ashkenazi Jewish (ASJ)

AF:

0.0416

AC:

1059

AN:

25464

East Asian (EAS)

AF:

0.0127

AC:

502

AN:

39454

South Asian (SAS)

AF:

0.0481

AC:

4102

AN:

85366

European-Finnish (FIN)

AF:

0.0682

AC:

3601

AN:

52824

Middle Eastern (MID)

AF:

0.0383

AC:

218

AN:

5698

European-Non Finnish (NFE)

AF:

0.0417

AC:

46070

AN:

1103640

Other (OTH)

AF:

0.0447

AC:

2666

AN:

59672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

3491

6982

10474

13965

17456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0432

AC:

6581

AN:

152304

Hom.:

163

Cov.:

AF XY:

0.0429

AC XY:

3191

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0523

AC:

2173

AN:

41570

American (AMR)

AF:

0.0216

AC:

330

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3470

East Asian (EAS)

AF:

0.0137

AC:

AN:

5164

South Asian (SAS)

AF:

0.0497

AC:

240

AN:

4828

European-Finnish (FIN)

AF:

0.0651

AC:

692

AN:

10626

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0416

AC:

2827

AN:

68018

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

329

658

986

1315

1644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0368

Hom.:

Bravo

AF:

0.0410

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.54

(source)

DANN

Benign

0.64

PhyloP100

-1.1

PromoterAI

0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs2233810

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over