chr1-175527565-C-G

Variant names:

• chr1-175527565-C-G
• rs859365
• NM_003285.3:c.-64+704G>C

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+704G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,042 control chromosomes in the GnomAD database, including 3,846 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 0.21 (3846 hom., cov: 33)
• Consequence: TNR NM_003285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3	c.-64+704G>C		intron_variant	Intron 2 of 22	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.-959+704G>C		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+704G>C		intron_variant	Intron 2 of 22	5	NM_003285.3	ENSP00000356646.1
TNR	ENST00000713977.1	c.-64+704G>C		intron_variant	Intron 1 of 19			ENSP00000519268.1
TNR	ENST00000713978.1	n.-64+704G>C		intron_variant	Intron 1 of 12			ENSP00000519269.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31587 AN: 151922 Hom.: 3824 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.208 AC: 31652 AN: 152042 Hom.: 3846 Cov.: 33 AF XY: 0.204 AC XY: 15126 AN XY: 74320

African (AFR) AF: 0.327 AC: 13549 AN: 41466

American (AMR) AF: 0.134 AC: 2052 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3466

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5176

South Asian (SAS) AF: 0.148 AC: 710 AN: 4810

European-Finnish (FIN) AF: 0.175 AC: 1845 AN: 10548

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12589 AN: 67966

Other (OTH) AF: 0.174 AC: 368 AN: 2112

Alfa AF: 0.0908 Hom.: 115

Bravo AF: 0.206

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		-0.63
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: rs859365; hg19: chr1-175496701;