rs4651322

Variant names:

• chr1-175135583-T-C
• rs4651322
• NM_022093.2:c.3331-262T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022093.2(TNN):​c.3331-262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,158 control chromosomes in the GnomAD database, including 28,874 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 0.61 (28874 hom., cov: 33)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNN	NM_022093.2	c.3331-262T>C		intron_variant	Intron 15 of 18	ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2	c.3385-262T>C		intron_variant	Intron 15 of 18		XP_016857537.1
TNN	XM_017002049.2	c.3121-262T>C		intron_variant	Intron 14 of 17		XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9	c.3331-262T>C		intron_variant	Intron 15 of 18	2	NM_022093.2	ENSP00000239462.4
TNN	ENST00000621086.1	c.2800-262T>C		intron_variant	Intron 12 of 15	5		ENSP00000480895.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93469 AN: 152040 Hom.: 28844 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.615 AC: 93549 AN: 152158 Hom.: 28874 Cov.: 33 AF XY: 0.616 AC XY: 45830 AN XY: 74380

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.612

Alfa AF: 0.622 Hom.: 13433

Bravo AF: 0.614

Asia WGS AF: 0.583 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.49

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: rs4651322; hg19: chr1-175104719;