rs859395

Variant names:

• chr1-175492708-C-T
• rs859395
• NM_003285.3:c.-64+35561G>A

Variant summary

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

The NM_003285.3(TNR):​c.-64+35561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,872 control chromosomes in the GnomAD database, including 17,995 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 0.46 (17995 hom., cov: 31)
• Consequence: TNR NM_003285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 1 publications found

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]

TNR Gene-Disease associations (from GenCC):

• neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3	c.-64+35561G>A		intron_variant	Intron 2 of 22	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.-959+35561G>A		intron_variant	Intron 2 of 22		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7	c.-64+35561G>A		intron_variant	Intron 2 of 22	5	NM_003285.3	ENSP00000356646.1
TNR	ENST00000713977.1	c.-64+35561G>A		intron_variant	Intron 1 of 19			ENSP00000519268.1
TNR	ENST00000713978.1	n.-64+35561G>A		intron_variant	Intron 1 of 12			ENSP00000519269.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70152 AN: 151756 Hom.: 17963 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.462 AC: 70225 AN: 151872 Hom.: 17995 Cov.: 31 AF XY: 0.456 AC XY: 33876 AN XY: 74216

African (AFR) AF: 0.696 AC: 28819 AN: 41410

American (AMR) AF: 0.367 AC: 5594 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3468

East Asian (EAS) AF: 0.135 AC: 697 AN: 5168

South Asian (SAS) AF: 0.367 AC: 1762 AN: 4802

European-Finnish (FIN) AF: 0.395 AC: 4156 AN: 10526

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26886 AN: 67932

Other (OTH) AF: 0.411 AC: 866 AN: 2106

Alfa AF: 0.414 Hom.: 18221

Bravo AF: 0.466

Asia WGS AF: 0.234 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.051
DANN	Benign	0.62
PhyloP100		-1.5
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: rs859395; hg19: chr1-175461844;