rs11752495

chr6-32062138-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001365276.2(TNXB):c.7168+19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,604,262 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (99 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.181

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-32062138-G-T is Benign according to our data. Variant chr6-32062138-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 261153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32062138-G-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00525 (7619/1451952) while in subpopulation EAS AF= 0.0398 (1569/39460). AF 95% confidence interval is 0.0381. There are 99 homozygotes in gnomad4_exome. There are 4068 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNXB	NM_001365276.2	c.7168+19C>A		intron_variant		ENST00000644971.2
TNXB	NM_019105.8	c.7168+19C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2	c.7168+19C>A		intron_variant			NM_001365276.2
TNXB	ENST00000375244.7	c.7168+19C>A		intron_variant		5
TNXB	ENST00000647633.1	c.7909+19C>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.00485 AC: 738 AN: 152192 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00484

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00646 AC: 1545 AN: 239338 Hom.: 18 AF XY: 0.00717 AC XY: 937 AN XY: 130648

Gnomad AFR exome AF: 0.000718

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.0284

Gnomad EAS exome AF: 0.0114

Gnomad SAS exome AF: 0.0119

Gnomad FIN exome AF: 0.000521

Gnomad NFE exome AF: 0.00444

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.00525 AC: 7619 AN: 1451952 Hom.: 99 Cov.: 32 AF XY: 0.00564 AC XY: 4068 AN XY: 720708

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.00473

Gnomad4 ASJ exome AF: 0.0296

Gnomad4 EAS exome AF: 0.0398

Gnomad4 SAS exome AF: 0.0119

Gnomad4 FIN exome AF: 0.000690

Gnomad4 NFE exome AF: 0.00310

Gnomad4 OTH exome AF: 0.00653

GnomAD4 genome AF: 0.00484 AC: 737 AN: 152310 Hom.: 4 Cov.: 32 AF XY: 0.00533 AC XY: 397 AN XY: 74482

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00484

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00946 Hom.: 3

Bravo AF: 0.00521

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 24, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.6
Dann	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs11752495; hg19: chr6-32029915; COSMIC: COSV64490498; COSMIC: COSV64490498;