rs16847787

Positions:

• chr1-175074831-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.-35-2553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 152,270 control chromosomes in the GnomAD database, including 596 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 0.048 (596 hom., cov: 32)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNN	NM_022093.2	c.-35-2553C>T		intron_variant		ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2	c.19+1711C>T		intron_variant			XP_016857537.1
TNN	XM_017002049.2	c.19+1711C>T		intron_variant			XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9	c.-35-2553C>T		intron_variant		2	NM_022093.2	ENSP00000239462	P1

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7265 AN: 152152 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0267

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

GnomAD4 genome AF: 0.0478 AC: 7283 AN: 152270 Hom.: 596 Cov.: 32 AF XY: 0.0458 AC XY: 3413 AN XY: 74462

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0390 Hom.: 46

Bravo AF: 0.0542

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.64

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: rs16847787; hg19: chr1-175043967;