1-175140586-A-G

Variant names:

• chr1-175140586-A-G
• rs1018829
• NM_022093.2:c.3595+3598A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_022093.2(TNN):​c.3595+3598A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,156 control chromosomes in the GnomAD database, including 44,188 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 0.76 (44188 hom., cov: 33)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 7 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.776 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	NM_022093.2	MANE Select	c.3595+3598A>G		intron	N/A	NP_071376.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	ENST00000239462.9	TSL:2 MANE Select	c.3595+3598A>G		intron	N/A	ENSP00000239462.4
	TNN	ENST00000860455.1		c.3595+3598A>G		intron	N/A	ENSP00000530514.1
	TNN	ENST00000946425.1		c.3595+3598A>G		intron	N/A	ENSP00000616484.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115589 AN: 152038 Hom.: 44137 Cov.: 33

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.760 AC: 115693 AN: 152156 Hom.: 44188 Cov.: 33 AF XY: 0.760 AC XY: 56507 AN XY: 74386

African (AFR) AF: 0.763 AC: 31647 AN: 41504

American (AMR) AF: 0.781 AC: 11943 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2410 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2742 AN: 5170

South Asian (SAS) AF: 0.640 AC: 3080 AN: 4816

European-Finnish (FIN) AF: 0.778 AC: 8233 AN: 10588

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53156 AN: 67988

Other (OTH) AF: 0.762 AC: 1612 AN: 2116

Alfa AF: 0.767 Hom.: 142371

Bravo AF: 0.758

Asia WGS AF: 0.645 AC: 2240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	18
DANN	Benign	0.37
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1018829; hg19: chr1-175109722;