rs1385540

chr1-175366276-A-Cchr1-175366276-A-Gchr1-175366276-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003285.3(TNR):c.2054-138T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 885,400 control chromosomes in the GnomAD database, including 275,497 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 0.80 (48552 hom., cov: 33)
  • Exomes 𝑓: 0.78 (226945 hom.)
• Consequence: TNR NM_003285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712

Genes affected

TNR (HGNC:11953): (tenascin R) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The encoded protein is restricted to the central nervous system. The protein may play a role in neurite outgrowth, neural cell adhesion and modulation of sodium channel function. It is a constituent of perineuronal nets. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNR	NM_003285.3	c.2054-138T>G		intron_variant		ENST00000367674.7
TNR	NM_001328635.2	c.1055-138T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7	c.2054-138T>G		intron_variant		5	NM_003285.3	P1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121293 AN: 152068 Hom.: 48504 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.784 AC: 575066 AN: 733214 Hom.: 226945 AF XY: 0.783 AC XY: 285984 AN XY: 365118

Gnomad4 AFR exome AF: 0.843

Gnomad4 AMR exome AF: 0.826

Gnomad4 ASJ exome AF: 0.747

Gnomad4 EAS exome AF: 0.842

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.829

Gnomad4 NFE exome AF: 0.779

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.798 AC: 121397 AN: 152186 Hom.: 48552 Cov.: 33 AF XY: 0.799 AC XY: 59396 AN XY: 74370

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.792

Alfa AF: 0.781 Hom.: 23467

Bravo AF: 0.801

Asia WGS AF: 0.758 AC: 2634 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	11
Dann	Benign	0.46

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: rs1385540; hg19: chr1-175335412; COSMIC: COSV54880475;