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GeneBe

16-75647845-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018975.4(TERF2IP):c.-38C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,594,648 control chromosomes in the GnomAD database, including 40,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 8396 hom., cov: 33)
Exomes 𝑓: 0.15 ( 31761 hom. )

Consequence

TERF2IP
NM_018975.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.82
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-75647845-C-G is Benign according to our data. Variant chr16-75647845-C-G is described in ClinVar as [Benign]. Clinvar id is 1232920.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-75647845-C-G is described in Lovd as [Benign].
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TERF2IPNM_018975.4 linkuse as main transcriptc.-38C>G 5_prime_UTR_variant 1/3 ENST00000300086.5
TERF2IPXM_047434216.1 linkuse as main transcriptc.-38C>G 5_prime_UTR_variant 1/2
TERF2IPNR_144545.2 linkuse as main transcriptn.73C>G non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TERF2IPENST00000300086.5 linkuse as main transcriptc.-38C>G 5_prime_UTR_variant 1/31 NM_018975.4 P1
KARS1ENST00000566560.5 linkuse as main transcriptn.176+623G>C intron_variant, non_coding_transcript_variant 1
TERF2IPENST00000653858.1 linkuse as main transcriptc.-38C>G 5_prime_UTR_variant 1/4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.265
AC:
40306
AN:
152028
Hom.:
8372
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.500
Gnomad AMI
AF:
0.128
Gnomad AMR
AF:
0.350
Gnomad ASJ
AF:
0.178
Gnomad EAS
AF:
0.727
Gnomad SAS
AF:
0.352
Gnomad FIN
AF:
0.123
Gnomad MID
AF:
0.0955
Gnomad NFE
AF:
0.0920
Gnomad OTH
AF:
0.230
GnomAD3 exomes
AF:
0.257
AC:
61141
AN:
238124
Hom.:
13439
AF XY:
0.242
AC XY:
31357
AN XY:
129588
show subpopulations
Gnomad AFR exome
AF:
0.509
Gnomad AMR exome
AF:
0.457
Gnomad ASJ exome
AF:
0.158
Gnomad EAS exome
AF:
0.763
Gnomad SAS exome
AF:
0.326
Gnomad FIN exome
AF:
0.125
Gnomad NFE exome
AF:
0.0940
Gnomad OTH exome
AF:
0.194
GnomAD4 exome
AF:
0.150
AC:
216915
AN:
1442502
Hom.:
31761
Cov.:
31
AF XY:
0.152
AC XY:
109036
AN XY:
715390
show subpopulations
Gnomad4 AFR exome
AF:
0.510
Gnomad4 AMR exome
AF:
0.442
Gnomad4 ASJ exome
AF:
0.159
Gnomad4 EAS exome
AF:
0.752
Gnomad4 SAS exome
AF:
0.318
Gnomad4 FIN exome
AF:
0.126
Gnomad4 NFE exome
AF:
0.0927
Gnomad4 OTH exome
AF:
0.190
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.265
AC:
40392
AN:
152146
Hom.:
8396
Cov.:
33
AF XY:
0.273
AC XY:
20289
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.500
Gnomad4 AMR
AF:
0.351
Gnomad4 ASJ
AF:
0.178
Gnomad4 EAS
AF:
0.727
Gnomad4 SAS
AF:
0.351
Gnomad4 FIN
AF:
0.123
Gnomad4 NFE
AF:
0.0920
Gnomad4 OTH
AF:
0.232
Alfa
AF:
0.101
Hom.:
280
Bravo
AF:
0.296
Asia WGS
AF:
0.508
AC:
1763
AN:
3478

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 submitterclinical testingGeneDxJun 14, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
0.057
Dann
Benign
0.37

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.

Other links and lift over

dbSNP: rs1865493; hg19: chr16-75681743; COSMIC: COSV55614301; COSMIC: COSV55614301; API