Variant chr16-75647845-C-G 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.-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

Clinical Significance

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

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]

TERF2IP links:

KARS1 (HGNC:):

KARS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

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_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75647845-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
TERF2IP	NM_018975.4 linkuse as main transcript	c.-38C>G	5_prime_UTR_variant	1/3	ENST00000300086.5	NP_061848.2	Q9NYB0
TERF2IP	XM_047434216.1 linkuse as main transcript	c.-38C>G	5_prime_UTR_variant	1/2		XP_047290172.1
TERF2IP	NR_144545.2 linkuse as main transcript	n.73C>G	non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TERF2IP	ENST00000300086 linkuse as main transcript	c.-38C>G	5_prime_UTR_variant	1/3	1	NM_018975.4	ENSP00000300086.4	Q9NYB0
KARS1	ENST00000566560.5 linkuse as main transcript	n.176+623G>C	intron_variant		1
TERF2IP	ENST00000653858 linkuse as main transcript	c.-38C>G	5_prime_UTR_variant	1/4			ENSP00000499565.1	A0A590UJT3

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40306

AN:

152028

Hom.:

8372

Cov.:

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.:

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

AF:

0.265

AC:

40392

AN:

152146

Hom.:

8396

Cov.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.80

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.

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