chr1-175088986-C-T

Position:

• chr1-175088986-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022093.2(TNN):​c.1324+3492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,000 control chromosomes in the GnomAD database, including 23,491 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 0.55 (23491 hom., cov: 33)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

TNN (HGNC:22942): (tenascin N) Predicted to enable integrin binding activity. Predicted to be involved in several processes, including generation of neurons; negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation; and negative regulation of osteoblast differentiation. Predicted to act upstream of or within axonogenesis. Predicted to be located in extracellular matrix and neuron projection. Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNN	NM_022093.2	c.1324+3492C>T		intron_variant		ENST00000239462.9
TNN	XM_017002048.2	c.1378+3492C>T		intron_variant
TNN	XM_017002049.2	c.1378+3492C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNN	ENST00000239462.9	c.1324+3492C>T		intron_variant		2	NM_022093.2	P1
TNN	ENST00000621086.1	c.1324+3492C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83330 AN: 151882 Hom.: 23451 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.549 AC: 83431 AN: 152000 Hom.: 23491 Cov.: 33 AF XY: 0.545 AC XY: 40452 AN XY: 74278

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.554

Alfa AF: 0.530 Hom.: 3676

Bravo AF: 0.554

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.15

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: rs6681984; hg19: chr1-175058122;