rs17207986

Variant names:

• chr6-32111790-T-C
• rs17207986
• ENST00000442721.1:c.-9+3204A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32111790-T-C
• chr6-32111790-T-G

Variant summary

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

The ENST00000442721.1(TNXB):​c.-9+3204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 151,428 control chromosomes in the GnomAD database, including 250 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 0.046 (250 hom., cov: 32)
• Consequence: TNXB ENST00000442721.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 32 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)

ENSG00000286974 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000442721.1	c.-9+3204A>G		intron_variant	Intron 1 of 1	1		ENSP00000389946.1
ENSG00000286974	ENST00000656765.1	n.1426T>C		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000284829	ENST00000494022.1	n.289+4914A>G		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6958 AN: 151310 Hom.: 247 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.0180

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0441

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

GnomAD4 genome AF: 0.0461 AC: 6977 AN: 151428 Hom.: 250 Cov.: 32 AF XY: 0.0466 AC XY: 3443 AN XY: 73952

African (AFR) AF: 0.0137 AC: 565 AN: 41254

American (AMR) AF: 0.0367 AC: 558 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.0180 AC: 62 AN: 3454

East Asian (EAS) AF: 0.120 AC: 614 AN: 5138

South Asian (SAS) AF: 0.0758 AC: 361 AN: 4764

European-Finnish (FIN) AF: 0.0582 AC: 608 AN: 10454

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0597 AC: 4048 AN: 67846

Other (OTH) AF: 0.0498 AC: 105 AN: 2108

Alfa AF: 0.0510 Hom.: 625

Bravo AF: 0.0411

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.44
PhyloP100		-0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

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

Other links and lift over

dbSNP: rs17207986; hg19: chr6-32079567;