rs2395083

Positions:

• chr6-32043703-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001365276.2(TNXB):​c.11530+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,613,126 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 27)
  • Exomes 𝑓: 0.0036 (11 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.74

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-32043703-G-A is Benign according to our data. Variant chr6-32043703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.11530+46C>T		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.11524+46C>T		intron_variant			NP_061978.6
TNXB	NM_032470.4	c.817+46C>T		intron_variant			NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.11530+46C>T		intron_variant			NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 463 AN: 151952 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00325 AC: 813 AN: 250172 Hom.: 4 AF XY: 0.00366 AC XY: 496 AN XY: 135506

Gnomad AFR exome AF: 0.00162

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.000465

Gnomad NFE exome AF: 0.00311

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00362 AC: 5283 AN: 1461056 Hom.: 11 Cov.: 32 AF XY: 0.00376 AC XY: 2733 AN XY: 726854

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.000683

Gnomad4 NFE exome AF: 0.00347

Gnomad4 OTH exome AF: 0.00336

GnomAD4 genome AF: 0.00304 AC: 462 AN: 152070 Hom.: 1 Cov.: 27 AF XY: 0.00280 AC XY: 208 AN XY: 74356

Gnomad4 AFR AF: 0.00138

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00363

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00339 Hom.: 1

Bravo AF: 0.00323

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2395083; hg19: chr6-32011480;