Genetic Variant NM_017489.3:c.415+11T>G (chr8-73014001-T-G) – 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+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

Publications

10 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=-0.74).

BP6

Variant 8-73014001-T-G is Benign according to our data. Variant chr8-73014001-T-G is described in ClinVar as Benign. ClinVar VariationId 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.

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+11T>G	intron	N/A	NP_059523.2	P54274-1
TERF1	NM_001413364.1		c.415+11T>G	intron	N/A	NP_001400293.1
TERF1	NM_001410928.1		c.415+11T>G	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+11T>G	intron	N/A	ENSP00000276603.5	P54274-1
TERF1	ENST00000276602.10	TSL:1	c.415+11T>G	intron	N/A	ENSP00000276602.6	P54274-2
TERF1	ENST00000899325.1		c.415+11T>G	intron	N/A	ENSP00000569384.1

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

GnomAD2 exomes

AF:

0.628

AC:

153248

AN:

243932

AF XY:

0.636

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 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

African (AFR)

AF:

0.753

AC:

24234

AN:

32168

American (AMR)

AF:

0.451

AC:

19411

AN:

43076

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

18293

AN:

25696

East Asian (EAS)

AF:

0.306

AC:

12068

AN:

39390

South Asian (SAS)

AF:

0.592

AC:

49409

AN:

83440

European-Finnish (FIN)

AF:

0.683

AC:

36358

AN:

53252

Middle Eastern (MID)

AF:

0.743

AC:

3345

AN:

4500

European-Non Finnish (NFE)

AF:

0.695

AC:

744245

AN:

1071264

Other (OTH)

AF:

0.661

AC:

38713

AN:

58586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

14015

28030

42046

56061

70076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18404

36808

55212

73616

92020

<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:

0.677

AC:

102857

AN:

151872

Hom.:

35571

Cov.:

AF XY:

0.671

AC XY:

49817

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.743

AC:

30779

AN:

41412

American (AMR)

AF:

0.528

AC:

8062

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.698

AC:

2419

AN:

3468

East Asian (EAS)

AF:

0.320

AC:

1649

AN:

5160

South Asian (SAS)

AF:

0.591

AC:

2852

AN:

4826

European-Finnish (FIN)

AF:

0.697

AC:

7326

AN:

10514

Middle Eastern (MID)

AF:

0.767

AC:

224

AN:

292

European-Non Finnish (NFE)

AF:

0.701

AC:

47618

AN:

67924

Other (OTH)

AF:

0.689

AC:

1448

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1587

3173

4760

6346

7933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.699

Hom.:

11157

Bravo

AF:

0.666

Asia WGS

AF:

0.516

AC:

1792

AN:

3472

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

-0.74

CADD

Benign

8.7

(source)

DANN

Benign

0.66

PhyloP100

-1.3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over