chr6-32079491-T-C

Variant names:

• chr6-32079491-T-C
• rs17201560
• NM_001365276.2:c.4043-126A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001365276.2(TNXB):​c.4043-126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 805,102 control chromosomes in the GnomAD database, including 550 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 0.029 (80 hom., cov: 32)
  • Exomes 𝑓: 0.036 (470 hom.)
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0293 (4466/152264) while in subpopulation NFE AF= 0.0411 (2798/68004). AF 95% confidence interval is 0.0399. There are 80 homozygotes in gnomad4. There are 2140 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 80 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.4043-126A>G		intron_variant	Intron 10 of 43	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.4784-126A>G		intron_variant	Intron 11 of 44		NP_001415264.1
TNXB	NM_019105.8	c.4043-126A>G		intron_variant	Intron 10 of 43		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.4043-126A>G		intron_variant	Intron 10 of 43		NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.4784-126A>G		intron_variant	Intron 11 of 44			ENSP00000497649.1
TNXB	ENST00000375244.7	c.4043-126A>G		intron_variant	Intron 10 of 43	5		ENSP00000364393.3

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4460 AN: 152146 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0274

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0357 AC: 23302 AN: 652838 Hom.: 470 AF XY: 0.0355 AC XY: 11797 AN XY: 332380

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.0225

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.0191

Gnomad4 SAS exome AF: 0.0265

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0403

Gnomad4 OTH exome AF: 0.0313

GnomAD4 genome AF: 0.0293 AC: 4466 AN: 152264 Hom.: 80 Cov.: 32 AF XY: 0.0287 AC XY: 2140 AN XY: 74456

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0184

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0366 Hom.: 102

Bravo AF: 0.0267

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.51

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: rs17201560; hg19: chr6-32047268; COSMIC: COSV64480284; COSMIC: COSV64480284;