rs2018318

chr1-175146431-A-Cchr1-175146431-A-Gchr1-175146431-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022093.2(TNN):c.3760-500A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,120 control chromosomes in the GnomAD database, including 46,800 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 0.78 (46800 hom., cov: 33)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNN	NM_022093.2	c.3760-500A>C		intron_variant		ENST00000239462.9
TNN	XM_017002048.2	c.3814-500A>C		intron_variant
TNN	XM_017002049.2	c.3550-500A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNN	ENST00000239462.9	c.3760-500A>C		intron_variant		2	NM_022093.2	P1
TNN	ENST00000621086.1	c.3229-500A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118777 AN: 152002 Hom.: 46775 Cov.: 33

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.781 AC: 118850 AN: 152120 Hom.: 46800 Cov.: 33 AF XY: 0.783 AC XY: 58243 AN XY: 74362

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.797

Alfa AF: 0.801 Hom.: 6827

Bravo AF: 0.774

Asia WGS AF: 0.738 AC: 2563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	17
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: rs2018318; hg19: chr1-175115567;