rs2018318

Variant names:

• chr1-175146431-A-C
• rs2018318
• NM_022093.2:c.3760-500A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-175146431-A-C
• chr1-175146431-A-G
• chr1-175146431-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 rank	MANE	Protein	UniProt
TNN	NM_022093.2	c.3760-500A>C		intron_variant	Intron 18 of 18	ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2	c.3814-500A>C		intron_variant	Intron 18 of 18		XP_016857537.1
TNN	XM_017002049.2	c.3550-500A>C		intron_variant	Intron 17 of 17		XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9	c.3760-500A>C		intron_variant	Intron 18 of 18	2	NM_022093.2	ENSP00000239462.4
TNN	ENST00000621086.1	c.3229-500A>C		intron_variant	Intron 15 of 15	5		ENSP00000480895.1

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

African (AFR) AF: 0.681 AC: 28219 AN: 41454

American (AMR) AF: 0.830 AC: 12696 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2809 AN: 3468

East Asian (EAS) AF: 0.724 AC: 3746 AN: 5172

South Asian (SAS) AF: 0.728 AC: 3509 AN: 4820

European-Finnish (FIN) AF: 0.861 AC: 9123 AN: 10596

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56030 AN: 67994

Other (OTH) AF: 0.797 AC: 1684 AN: 2114

Alfa AF: 0.793 Hom.: 14840

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
PhyloP100		1.0
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: rs2018318; hg19: chr1-175115567;