rs2077580

Variant names:

• chr6-32053067-G-A
• rs2077580
• NM_001365276.2:c.8792-74C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32053067-G-A
• chr6-32053067-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365276.2(TNXB):​c.8792-74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 1,499,794 control chromosomes in the GnomAD database, including 6,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (825 hom., cov: 31)
  • Exomes 𝑓: 0.086 (5698 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.337
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-32053067-G-A is Benign according to our data. Variant chr6-32053067-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.8792-74C>T		intron_variant	Intron 25 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.9533-74C>T		intron_variant	Intron 26 of 44		NP_001415264.1
TNXB	NM_019105.8	c.8786-74C>T		intron_variant	Intron 25 of 43		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.8792-74C>T		intron_variant	Intron 25 of 43		NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.9533-74C>T		intron_variant	Intron 26 of 44			ENSP00000497649.1
TNXB	ENST00000375244.7	c.8792-74C>T		intron_variant	Intron 25 of 43	5		ENSP00000364393.3

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14785 AN: 152020 Hom.: 830 Cov.: 31

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0912

GnomAD4 exome AF: 0.0862 AC: 116188 AN: 1347656 Hom.: 5698 AF XY: 0.0870 AC XY: 58001 AN XY: 666622

African (AFR) AF: 0.150 AC: 4665 AN: 31200

American (AMR) AF: 0.0479 AC: 1825 AN: 38132

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2312 AN: 22534

East Asian (EAS) AF: 0.0206 AC: 801 AN: 38804

South Asian (SAS) AF: 0.130 AC: 9916 AN: 76014

European-Finnish (FIN) AF: 0.0533 AC: 2088 AN: 39182

Middle Eastern (MID) AF: 0.0740 AC: 404 AN: 5462

European-Non Finnish (NFE) AF: 0.0856 AC: 88990 AN: 1040098

Other (OTH) AF: 0.0922 AC: 5187 AN: 56230

GnomAD4 genome AF: 0.0972 AC: 14790 AN: 152138 Hom.: 825 Cov.: 31 AF XY: 0.0958 AC XY: 7122 AN XY: 74370

African (AFR) AF: 0.142 AC: 5870 AN: 41452

American (AMR) AF: 0.0495 AC: 757 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5178

South Asian (SAS) AF: 0.151 AC: 727 AN: 4822

European-Finnish (FIN) AF: 0.0537 AC: 570 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5977 AN: 67994

Other (OTH) AF: 0.0903 AC: 191 AN: 2116

Alfa AF: 0.0930 Hom.: 1889

Bravo AF: 0.0994

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		-0.34
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: rs2077580; hg19: chr6-32020844;