Variant 1-175330113-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003285.3(TNR):c.3754C>T(p.Leu1252=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,611,056 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 20 hom. )

Consequence

TNR
NM_003285.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.38

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-175330113-G-A is Benign according to our data. Variant chr1-175330113-G-A is described in ClinVar as [Benign]. Clinvar id is 708860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-175330113-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.38 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00247 (377/152372) while in subpopulation NFE AF= 0.00341 (232/68032). AF 95% confidence interval is 0.00305. There are 2 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 377 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNR	NM_003285.3 linkuse as main transcript	c.3754C>T	p.Leu1252=	synonymous_variant	21/23	ENST00000367674.7
LOC105371623	XR_001738299.2 linkuse as main transcript	n.318+603G>A		intron_variant, non_coding_transcript_variant
TNR	NM_001328635.2 linkuse as main transcript	c.2755C>T	p.Leu919=	synonymous_variant	21/23
LOC105371623	XR_001738302.2 linkuse as main transcript	n.232-3209G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7 linkuse as main transcript	c.3754C>T	p.Leu1252=	synonymous_variant	21/23	5	NM_003285.3	P1	Q92752-1
	ENST00000569593.1 linkuse as main transcript	n.336-264G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

377

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00313

AC:

784

AN:

250556

Hom.:

AF XY:

0.00300

AC XY:

406

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00354

Gnomad OTH exome

AF:

0.00639

GnomAD4 exome

AF:

0.00336

AC:

4894

AN:

1458684

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

2353

AN XY:

725016

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00336

Gnomad4 ASJ exome

AF:

0.0183

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00127

Gnomad4 NFE exome

AF:

0.00342

Gnomad4 OTH exome

AF:

0.00445

GnomAD4 genome

AF:

0.00247

AC:

377

AN:

152372

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00430

Hom.:

Bravo

AF:

0.00261

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00404

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	TNR: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.9

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over