chr1-175527565-C-G

Position:

• chr1-175527565-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	UniProt
TNR	NM_003285.3	c.-64+704G>C		intron_variant		ENST00000367674.7
TNR	NM_001328635.2	c.-959+704G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7	c.-64+704G>C		intron_variant		5	NM_003285.3	P1

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.174

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

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: rs859365; hg19: chr1-175496701;