rs2228359

Positions:

• chr1-175355515-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003285.3(TNR):​c.3237T>C​(p.Asp1079=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,613,486 control chromosomes in the GnomAD database, including 383,955 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 0.65 (32655 hom., cov: 32)
  • Exomes 𝑓: 0.69 (351300 hom.)
• Consequence: TNR NM_003285.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.951 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNR	NM_003285.3	c.3237T>C	p.Asp1079=	synonymous_variant	17/23	ENST00000367674.7
TNR	NM_001328635.2	c.2238T>C	p.Asp746=	synonymous_variant	17/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7	c.3237T>C	p.Asp1079=	synonymous_variant	17/23	5	NM_003285.3	P1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98752 AN: 151938 Hom.: 32628 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.638

GnomAD3 exomes AF: 0.697 AC: 174673 AN: 250766 Hom.: 61435 AF XY: 0.695 AC XY: 94206 AN XY: 135482

Gnomad AFR exome AF: 0.536

Gnomad AMR exome AF: 0.756

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.816

Gnomad SAS exome AF: 0.679

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.684

Gnomad OTH exome AF: 0.685

GnomAD4 exome AF: 0.692 AC: 1011000 AN: 1461430 Hom.: 351300 Cov.: 57 AF XY: 0.691 AC XY: 502577 AN XY: 726998

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.837

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.690

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.650 AC: 98828 AN: 152056 Hom.: 32655 Cov.: 32 AF XY: 0.655 AC XY: 48677 AN XY: 74328

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.643

Alfa AF: 0.675 Hom.: 39905

Bravo AF: 0.644

Asia WGS AF: 0.721 AC: 2508 AN: 3478

EpiCase AF: 0.669

EpiControl AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.68
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: rs2228359; hg19: chr1-175324651; COSMIC: COSV54901946;