rs2269426

Variant names:

• chr6-32108722-G-A
• rs2269426
• NM_001365276.2:c.-9+459C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32108722-G-A
• chr6-32108722-G-C
• chr6-32108722-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365276.2(TNXB):​c.-9+459C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,994 control chromosomes in the GnomAD database, including 9,743 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 0.35 (9743 hom., cov: 31)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 68 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome due to tenascin-X deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina, PanelApp Australia, Orphanet
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• vesicoureteral reflux 8

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000284829 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.-9+459C>T		intron_variant	Intron 1 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.-9+459C>T		intron_variant	Intron 1 of 44		NP_001415264.1
TNXB	NM_019105.8	c.-9+459C>T		intron_variant	Intron 1 of 43		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.-9+459C>T		intron_variant	Intron 1 of 43		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52578 AN: 151874 Hom.: 9748 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.346 AC: 52590 AN: 151994 Hom.: 9743 Cov.: 31 AF XY: 0.349 AC XY: 25927 AN XY: 74280

African (AFR) AF: 0.240 AC: 9959 AN: 41458

American (AMR) AF: 0.370 AC: 5657 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3472

East Asian (EAS) AF: 0.249 AC: 1284 AN: 5152

South Asian (SAS) AF: 0.343 AC: 1651 AN: 4818

European-Finnish (FIN) AF: 0.440 AC: 4649 AN: 10570

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.384 AC: 26092 AN: 67926

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.366 Hom.: 28325

Bravo AF: 0.339

Asia WGS AF: 0.287 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.096
DANN	Benign	0.69
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2269426; hg19: chr6-32076499;