rs1385540

Variant names:

• chr1-175366276-A-C
• rs1385540
• NM_003285.3:c.2054-138T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-175366276-A-C
• chr1-175366276-A-G
• chr1-175366276-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003285.3. 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
	TNR	NM_003285.3	MANE Select	c.2054-138T>G		intron	N/A	NP_003276.3
	TNR	NM_001328635.2		c.1055-138T>G		intron	N/A	NP_001315564.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNR	ENST00000367674.7	TSL:5 MANE Select	c.2054-138T>G		intron	N/A	ENSP00000356646.1
	TNR	ENST00000713954.1		c.2054-138T>G		intron	N/A	ENSP00000519247.1
	TNR	ENST00000713977.1		c.1313-138T>G		intron	N/A	ENSP00000519268.1

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

African (AFR) AF: 0.843 AC: 14687 AN: 17426

American (AMR) AF: 0.826 AC: 13272 AN: 16072

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 10930 AN: 14628

East Asian (EAS) AF: 0.842 AC: 26151 AN: 31068

South Asian (SAS) AF: 0.742 AC: 26445 AN: 35654

European-Finnish (FIN) AF: 0.829 AC: 31453 AN: 37922

Middle Eastern (MID) AF: 0.736 AC: 2316 AN: 3146

European-Non Finnish (NFE) AF: 0.779 AC: 422711 AN: 542686

Other (OTH) AF: 0.783 AC: 27101 AN: 34612

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

African (AFR) AF: 0.835 AC: 34687 AN: 41540

American (AMR) AF: 0.818 AC: 12501 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2600 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4178 AN: 5172

South Asian (SAS) AF: 0.731 AC: 3519 AN: 4816

European-Finnish (FIN) AF: 0.823 AC: 8711 AN: 10584

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52657 AN: 68000

Other (OTH) AF: 0.792 AC: 1673 AN: 2112

Alfa AF: 0.783 Hom.: 26163

Bravo AF: 0.801

Asia WGS AF: 0.758 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.46
PhyloP100		0.71
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: rs1385540; hg19: chr1-175335412; COSMIC: COSV54880475;