Genetic Variant TERF1:c.415+218C>T (chr8-73014208-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017489.3(TERF1):c.415+218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 145,530 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 186 hom., cov: 31)

Consequence

TERF1
NM_017489.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.164

Publications

0 publications found

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:

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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=-0.85).

BP6

Variant 8-73014208-C-T is Benign according to our data. Variant chr8-73014208-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017489.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TERF1	NM_017489.3	MANE Select	c.415+218C>T	intron	N/A	NP_059523.2	P54274-1
TERF1	NM_001413364.1		c.415+218C>T	intron	N/A	NP_001400293.1
TERF1	NM_001410928.1		c.415+218C>T	intron	N/A	NP_001397857.1	A0A7I2YQE7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TERF1	ENST00000276603.10	TSL:1 MANE Select	c.415+218C>T	intron	N/A	ENSP00000276603.5	P54274-1
TERF1	ENST00000276602.10	TSL:1	c.415+218C>T	intron	N/A	ENSP00000276602.6	P54274-2
TERF1	ENST00000899325.1		c.415+218C>T	intron	N/A	ENSP00000569384.1

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4193

AN:

145418

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.000873

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000678

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000373

Gnomad OTH

AF:

0.0213

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0290

AC:

4217

AN:

145530

Hom.:

186

Cov.:

AF XY:

0.0280

AC XY:

1977

AN XY:

70502

show subpopulations

African (AFR)

AF:

0.102

AC:

3982

AN:

38862

American (AMR)

AF:

0.0116

AC:

162

AN:

13960

Ashkenazi Jewish (ASJ)

AF:

0.000873

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

4836

South Asian (SAS)

AF:

0.000679

AC:

AN:

4416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000373

AC:

AN:

67038

Other (OTH)

AF:

0.0210

AC:

AN:

1998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

198

396

593

791

989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0249

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

(source)

DANN

Benign

0.71

PhyloP100

-0.16

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over