dbSNP rs10107605: TERF1:n.170A>C (chr8-73030122-A-C) – 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 ENST00000518961.1(TERF1):n.170A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 375,148 control chromosomes in the GnomAD database, including 2,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 816 hom., cov: 32)

Exomes 𝑓: 0.12 ( 1723 hom. )

Consequence

TERF1
ENST00000518961.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.168

Publications

11 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:

Genome browser will be placed here

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=-0.79).

BP6

Variant 8-73030122-A-C is Benign according to our data. Variant chr8-73030122-A-C is described in ClinVar as Benign. ClinVar VariationId is 1233718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3 link	c.888-214A>C		intron_variant	Intron 6 of 9	ENST00000276603.10	NP_059523.2	P54274-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10 link	c.888-214A>C		intron_variant	Intron 6 of 9	1	NM_017489.3	ENSP00000276603.5		P54274-1

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14193

AN:

152100

Hom.:

815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0934

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.118

AC:

26252

AN:

222930

Hom.:

1723

Cov.:

AF XY:

0.119

AC XY:

13559

AN XY:

113800

show subpopulations

African (AFR)

AF:

0.0246

AC:

160

AN:

6508

American (AMR)

AF:

0.0908

AC:

589

AN:

6484

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

1188

AN:

8134

East Asian (EAS)

AF:

0.118

AC:

2342

AN:

19804

South Asian (SAS)

AF:

0.109

AC:

427

AN:

3920

European-Finnish (FIN)

AF:

0.106

AC:

1987

AN:

18778

Middle Eastern (MID)

AF:

0.163

AC:

192

AN:

1176

European-Non Finnish (NFE)

AF:

0.123

AC:

17660

AN:

143280

Other (OTH)

AF:

0.115

AC:

1707

AN:

14846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1043

2087

3130

4174

5217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0932

AC:

14186

AN:

152218

Hom.:

816

Cov.:

AF XY:

0.0942

AC XY:

7008

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0225

AC:

935

AN:

41554

American (AMR)

AF:

0.0930

AC:

1422

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

486

AN:

3470

East Asian (EAS)

AF:

0.111

AC:

572

AN:

5176

South Asian (SAS)

AF:

0.125

AC:

601

AN:

4820

European-Finnish (FIN)

AF:

0.122

AC:

1286

AN:

10576

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8503

AN:

68012

Other (OTH)

AF:

0.118

AC:

250

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

649

1298

1948

2597

3246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.112

Hom.:

733

Bravo

AF:

0.0892

Asia WGS

AF:

0.151

AC:

524

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 15, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.5

(source)

DANN

Benign

0.86

PhyloP100

-0.17

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over