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GeneBe

rs34368910

chr8-73046075-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_017489.3(TERF1):c.1258T>C(p.Leu420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,610,046 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00098 ( 12 hom. )

Consequence

TERF1
NM_017489.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.355
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-73046075-T-C is Benign according to our data. Variant chr8-73046075-T-C is described in ClinVar as [Benign]. Clinvar id is 784130.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.355 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00691 (1052/152302) while in subpopulation AFR AF= 0.0233 (967/41556). AF 95% confidence interval is 0.0221. There are 8 homozygotes in gnomad4. There are 519 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1050 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TERF1NM_017489.3 linkuse as main transcriptc.1258T>C p.Leu420= synonymous_variant 10/10 ENST00000276603.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TERF1ENST00000276603.10 linkuse as main transcriptc.1258T>C p.Leu420= synonymous_variant 10/101 NM_017489.3 P4P54274-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00690
AC:
1050
AN:
152184
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0233
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.00812
GnomAD3 exomes
AF:
0.00197
AC:
477
AN:
242158
Hom.:
8
AF XY:
0.00147
AC XY:
193
AN XY:
131178
show subpopulations
Gnomad AFR exome
AF:
0.0245
Gnomad AMR exome
AF:
0.00169
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000140
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000297
Gnomad OTH exome
AF:
0.00119
GnomAD4 exome
AF:
0.000980
AC:
1428
AN:
1457744
Hom.:
12
Cov.:
30
AF XY:
0.000885
AC XY:
642
AN XY:
725140
show subpopulations
Gnomad4 AFR exome
AF:
0.0282
Gnomad4 AMR exome
AF:
0.00204
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000105
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000203
Gnomad4 OTH exome
AF:
0.00232
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00691
AC:
1052
AN:
152302
Hom.:
8
Cov.:
32
AF XY:
0.00697
AC XY:
519
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0233
Gnomad4 AMR
AF:
0.00275
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00803
Alfa
AF:
0.00459
Hom.:
1
Bravo
AF:
0.00832
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000388
EpiControl
AF:
0.000481

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 testingInvitaeJul 10, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
Cadd
Benign
6.8
Dann
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs34368910; hg19: chr8-73958310; API