Genetic Variant NM_017489.3:c.887+71C>T (chr8-73027123-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017489.3(TERF1):c.887+71C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,073,736 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 59 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 29 hom. )

Consequence

TERF1
NM_017489.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0330

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-73027123-C-T is Benign according to our data. Variant chr8-73027123-C-T is described in ClinVar as Benign. ClinVar VariationId is 1174354.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 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.887+71C>T	intron	N/A	NP_059523.2	P54274-1
TERF1	NM_001413364.1		c.887+71C>T	intron	N/A	NP_001400293.1
TERF1	NM_001410928.1		c.887+71C>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.887+71C>T	intron	N/A	ENSP00000276603.5	P54274-1
TERF1	ENST00000276602.10	TSL:1	c.887+71C>T	intron	N/A	ENSP00000276602.6	P54274-2
TERF1	ENST00000899325.1		c.887+71C>T	intron	N/A	ENSP00000569384.1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2384

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00140

AC:

1286

AN:

921612

Hom.:

AF XY:

0.00117

AC XY:

550

AN XY:

470110

show subpopulations

African (AFR)

AF:

0.0521

AC:

1072

AN:

20564

American (AMR)

AF:

0.00277

AC:

AN:

24210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19820

East Asian (EAS)

AF:

0.00

AC:

AN:

32988

South Asian (SAS)

AF:

0.0000480

AC:

AN:

62532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37222

Middle Eastern (MID)

AF:

0.000827

AC:

AN:

3626

European-Non Finnish (NFE)

AF:

0.0000309

AC:

AN:

678830

Other (OTH)

AF:

0.00287

AC:

120

AN:

41820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.0157

AC:

2382

AN:

152124

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1122

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0548

AC:

2273

AN:

41494

American (AMR)

AF:

0.00524

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67978

Other (OTH)

AF:

0.0109

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

115

230

345

460

575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0151

Hom.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.00347

AC:

AN:

3468

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.4

(source)

DANN

Benign

0.36

PhyloP100

0.033

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over