dbSNP rs7774197: TNXB:c.4375+535T>G (chr6-32078498-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_001365276.2(TNXB):c.4375+535T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,998 control chromosomes in the GnomAD database, including 915 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 0.098 ( 911 hom., cov: 31)

Exomes 𝑓: 0.037 ( 4 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Publications

40 publications found

Variant links:

Genes affected

TNXB (HGNC:11976): (tenascin XB) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TNXB links:

ENSG00000294466 (HGNC:):

ENSG00000294466 links:

RNA5SP206 (HGNC:43106): (RNA, 5S ribosomal pseudogene 206)

RNA5SP206 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=-0.74).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.4375+535T>G	intron_variant	Intron 11 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.5116+535T>G	intron_variant	Intron 12 of 44		NP_001415264.1
TNXB	NM_019105.8 link	c.4375+535T>G	intron_variant	Intron 11 of 43		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.4375+535T>G		intron_variant	Intron 11 of 43		NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0978

AC:

14788

AN:

151140

Hom.:

909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0730

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.0818

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0634

Gnomad OTH

AF:

0.0851

GnomAD4 exome

AF:

0.0370

AC:

AN:

1758

Hom.:

Cov.:

AF XY:

0.0410

AC XY:

AN XY:

1000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0139

AC:

AN:

European-Finnish (FIN)

AF:

0.0972

AC:

AN:

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0348

AC:

AN:

1408

Other (OTH)

AF:

0.0648

AC:

AN:

108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0978

AC:

14796

AN:

151240

Hom.:

911

Cov.:

AF XY:

0.0999

AC XY:

7373

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.163

AC:

6712

AN:

41086

American (AMR)

AF:

0.0728

AC:

1107

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3466

East Asian (EAS)

AF:

0.0814

AC:

418

AN:

5134

South Asian (SAS)

AF:

0.0394

AC:

189

AN:

4800

European-Finnish (FIN)

AF:

0.170

AC:

1752

AN:

10322

Middle Eastern (MID)

AF:

0.0479

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0634

AC:

4304

AN:

67916

Other (OTH)

AF:

0.0847

AC:

178

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

631

1261

1892

2522

3153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.0690

Hom.:

2035

Bravo

AF:

0.0963

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.7

(source)

DANN

Benign

0.55

PhyloP100

-0.0030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over