Variant chr8-73014001-T-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_017489.3(TERF1):c.415+11T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,563,244 control chromosomes in the GnomAD database, including 358,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35571 hom., cov: 31)

Exomes 𝑓: 0.67 ( 322691 hom. )

Consequence

TERF1
NM_017489.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

TERF1 (HGNC:11728): (telomeric repeat binding factor 1) This gene encodes a telomere specific protein which is a component of the telomere nucleoprotein complex. This protein is present at telomeres throughout the cell cycle and functions as an inhibitor of telomerase, acting in cis to limit the elongation of individual chromosome ends. The protein structure contains a C-terminal Myb motif, a dimerization domain near its N-terminus and an acidic N-terminus. Multiple transcripts of this gene are alternatively spliced products. [provided by RefSeq, Aug 2022]

TERF1 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=-0.74).

BP6

Variant 8-73014001-T-G is Benign according to our data. Variant chr8-73014001-T-G is described in ClinVar as [Benign]. Clinvar id is 1294455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF1	NM_017489.3 linkuse as main transcript	c.415+11T>G		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10 linkuse as main transcript	c.415+11T>G		intron_variant		1	NM_017489.3	P4	P54274-1

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102772

AN:

151754

Hom.:

35544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.743

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.698

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.697

Gnomad MID

AF:

0.774

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.686

GnomAD3 exomes

AF:

0.628

AC:

153248

AN:

243932

Hom.:

50280

AF XY:

0.636

AC XY:

83990

AN XY:

132154

show subpopulations

Gnomad AFR exome

AF:

0.745

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.705

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.601

Gnomad FIN exome

AF:

0.689

Gnomad NFE exome

AF:

0.704

Gnomad OTH exome

AF:

0.672

GnomAD4 exome

AF:

0.670

AC:

946076

AN:

1411372

Hom.:

322691

Cov.:

AF XY:

0.670

AC XY:

471770

AN XY:

704626

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.451

Gnomad4 ASJ exome

AF:

0.712

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.592

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.695

Gnomad4 OTH exome

AF:

0.661

GnomAD4 genome

AF:

0.677

AC:

102857

AN:

151872

Hom.:

35571

Cov.:

AF XY:

0.671

AC XY:

49817

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.743

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.698

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.697

Gnomad4 NFE

AF:

0.701

Gnomad4 OTH

AF:

0.689

Alfa

AF:

0.698

Hom.:

10936

Bravo

AF:

0.666

Asia WGS

AF:

0.516

AC:

1792

AN:

3472

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

-0.74

CADD

Benign

8.7

DANN

Benign

0.66

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