1-175124889-G-A

Variant names:

• chr1-175124889-G-A
• rs12094153
• NM_022093.2:c.2914+1226G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022093.2(TNN):​c.2914+1226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,348 control chromosomes in the GnomAD database, including 9,716 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 0.35 (9716 hom., cov: 32)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022093.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	NM_022093.2	MANE Select	c.2914+1226G>A		intron	N/A	NP_071376.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	ENST00000239462.9	TSL:2 MANE Select	c.2914+1226G>A		intron	N/A	ENSP00000239462.4
	TNN	ENST00000621086.1	TSL:5	c.2383+1226G>A		intron	N/A	ENSP00000480895.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52623 AN: 151230 Hom.: 9711 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.348 AC: 52650 AN: 151348 Hom.: 9716 Cov.: 32 AF XY: 0.345 AC XY: 25519 AN XY: 73894

African (AFR) AF: 0.279 AC: 11491 AN: 41142

American (AMR) AF: 0.280 AC: 4254 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3460

East Asian (EAS) AF: 0.0891 AC: 459 AN: 5154

South Asian (SAS) AF: 0.205 AC: 981 AN: 4790

European-Finnish (FIN) AF: 0.469 AC: 4892 AN: 10428

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28554 AN: 67870

Other (OTH) AF: 0.339 AC: 713 AN: 2102

Alfa AF: 0.373 Hom.: 7370

Bravo AF: 0.328

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.14
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12094153; hg19: chr1-175094025;