dbSNP rs1385540: TNR:c.2054-138T>G (chr1-175366276-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003285.3(TNR):c.2054-138T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 885,400 control chromosomes in the GnomAD database, including 275,497 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 48552 hom., cov: 33)

Exomes 𝑓: 0.78 ( 226945 hom. )

Consequence

TNR
NM_003285.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.712

Publications

10 publications found

Variant links:

Genes affected

TNR (HGNC:11953): (tenascin R) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The encoded protein is restricted to the central nervous system. The protein may play a role in neurite outgrowth, neural cell adhesion and modulation of sodium channel function. It is a constituent of perineuronal nets. [provided by RefSeq, Aug 2013]

TNR Gene-Disease associations (from GenCC):

neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

TNR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3 link	c.2054-138T>G		intron_variant	Intron 10 of 22	ENST00000367674.7	NP_003276.3	Q92752-1A1L306
TNR	NM_001328635.2 link	c.1055-138T>G		intron_variant	Intron 10 of 22		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7 link	c.2054-138T>G		intron_variant	Intron 10 of 22	5	NM_003285.3	ENSP00000356646.1		Q92752-1

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121293

AN:

152068

Hom.:

48504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.823

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.774

Gnomad OTH

AF:

0.789

GnomAD4 exome

AF:

0.784

AC:

575066

AN:

733214

Hom.:

226945

AF XY:

0.783

AC XY:

285984

AN XY:

365118

show subpopulations

African (AFR)

AF:

0.843

AC:

14687

AN:

17426

American (AMR)

AF:

0.826

AC:

13272

AN:

16072

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

10930

AN:

14628

East Asian (EAS)

AF:

0.842

AC:

26151

AN:

31068

South Asian (SAS)

AF:

0.742

AC:

26445

AN:

35654

European-Finnish (FIN)

AF:

0.829

AC:

31453

AN:

37922

Middle Eastern (MID)

AF:

0.736

AC:

2316

AN:

3146

European-Non Finnish (NFE)

AF:

0.779

AC:

422711

AN:

542686

Other (OTH)

AF:

0.783

AC:

27101

AN:

34612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6025

12050

18076

24101

30126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8404

16808

25212

33616

42020

<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:

0.798

AC:

121397

AN:

152186

Hom.:

48552

Cov.:

AF XY:

0.799

AC XY:

59396

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.835

AC:

34687

AN:

41540

American (AMR)

AF:

0.818

AC:

12501

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

2600

AN:

3472

East Asian (EAS)

AF:

0.808

AC:

4178

AN:

5172

South Asian (SAS)

AF:

0.731

AC:

3519

AN:

4816

European-Finnish (FIN)

AF:

0.823

AC:

8711

AN:

10584

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.774

AC:

52657

AN:

68000

Other (OTH)

AF:

0.792

AC:

1673

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1308

2616

3925

5233

6541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.783

Hom.:

26163

Bravo

AF:

0.801

Asia WGS

AF:

0.758

AC:

2634

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

0.71

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

Computational scores

Splicing

Publications

Other links and lift over