chr6-32078498-A-C

Variant names:

• chr6-32078498-A-C
• rs7774197
• NM_001365276.2:c.4375+535T>G

Variant summary

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

The NM_001365276.2(TNXB):​c.4375+535T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,998 control chromosomes in the GnomAD database, including 915 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 0.098 (911 hom., cov: 31)
  • Exomes 𝑓: 0.037 (4 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 40 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]

ENSG00000294466 (HGNC:):

RNA5SP206 (HGNC:43106): (RNA, 5S ribosomal pseudogene 206)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

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.4375+535T>G		intron	N/A	NP_001352205.1
	TNXB	NM_001428335.1		c.5116+535T>G		intron	N/A	NP_001415264.1
	TNXB	NM_019105.8		c.4375+535T>G		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.4375+535T>G		intron	N/A	ENSP00000496448.1
	TNXB	ENST00000647633.1		c.5116+535T>G		intron	N/A	ENSP00000497649.1
	TNXB	ENST00000375244.7	TSL:5	c.4375+535T>G		intron	N/A	ENSP00000364393.3

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14788 AN: 151140 Hom.: 909 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0851

GnomAD4 exome AF: 0.0370 AC: 65 AN: 1758 Hom.: 4 Cov.: 0 AF XY: 0.0410 AC XY: 41 AN XY: 1000

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.00 AC: 0 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 32

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.0139 AC: 1 AN: 72

European-Finnish (FIN) AF: 0.0972 AC: 7 AN: 72

Middle Eastern (MID) AF: 0.125 AC: 1 AN: 8

European-Non Finnish (NFE) AF: 0.0348 AC: 49 AN: 1408

Other (OTH) AF: 0.0648 AC: 7 AN: 108

GnomAD4 genome AF: 0.0978 AC: 14796 AN: 151240 Hom.: 911 Cov.: 31 AF XY: 0.0999 AC XY: 7373 AN XY: 73812

African (AFR) AF: 0.163 AC: 6712 AN: 41086

American (AMR) AF: 0.0728 AC: 1107 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3466

East Asian (EAS) AF: 0.0814 AC: 418 AN: 5134

South Asian (SAS) AF: 0.0394 AC: 189 AN: 4800

European-Finnish (FIN) AF: 0.170 AC: 1752 AN: 10322

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0634 AC: 4304 AN: 67916

Other (OTH) AF: 0.0847 AC: 178 AN: 2102

Alfa AF: 0.0690 Hom.: 2035

Bravo AF: 0.0963

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.7
DANN	Benign	0.55
PhyloP100		-0.0030
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: rs7774197; hg19: chr6-32046275;