rs2856450

Variant names:

• chr6-32044177-T-A
• rs2856450
• NM_001365276.2:c.11264-48A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32044177-T-A
• chr6-32044177-T-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365276.2(TNXB):​c.11264-48A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,317,606 control chromosomes in the GnomAD database, including 8 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 0.000066 (2 hom., cov: 18)
  • Exomes 𝑓: 0.000058 (6 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 1 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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	NM_001365276.2	MANE Select	c.11264-48A>T		intron	N/A	NP_001352205.1
	TNXB	NM_001428335.1		c.12005-48A>T		intron	N/A	NP_001415264.1
	TNXB	NM_019105.8		c.11258-48A>T		intron	N/A	NP_061978.6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	ENST00000644971.2	MANE Select	c.11264-48A>T		intron	N/A	ENSP00000496448.1
	TNXB	ENST00000451343.4	TSL:1	c.551-48A>T		intron	N/A	ENSP00000407685.1
	TNXB	ENST00000490077.5	TSL:1	n.1091-48A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 7 AN: 106604 Hom.: 2 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000186

Gnomad ASJ AF: 0.00190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000998 AC: 18 AN: 180354 AF XY: 0.000113

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00224

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000578 AC: 70 AN: 1211002 Hom.: 6 Cov.: 31 AF XY: 0.0000563 AC XY: 34 AN XY: 603852

African (AFR) AF: 0.00 AC: 0 AN: 27834

American (AMR) AF: 0.00 AC: 0 AN: 35504

Ashkenazi Jewish (ASJ) AF: 0.00198 AC: 46 AN: 23290

East Asian (EAS) AF: 0.00 AC: 0 AN: 36104

South Asian (SAS) AF: 0.00 AC: 0 AN: 70704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3766

European-Non Finnish (NFE) AF: 0.0000175 AC: 16 AN: 916500

Other (OTH) AF: 0.000156 AC: 8 AN: 51150

GnomAD4 genome AF: 0.0000657 AC: 7 AN: 106604 Hom.: 2 Cov.: 18 AF XY: 0.0000584 AC XY: 3 AN XY: 51370

African (AFR) AF: 0.00 AC: 0 AN: 27026

American (AMR) AF: 0.000186 AC: 2 AN: 10776

Ashkenazi Jewish (ASJ) AF: 0.00190 AC: 5 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3818

South Asian (SAS) AF: 0.00 AC: 0 AN: 3068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49950

Other (OTH) AF: 0.00 AC: 0 AN: 1472

Alfa AF: 0.00 Hom.: 209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.52
PhyloP100		-1.1

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: rs2856450; hg19: chr6-32011954;