chr1-175074831-C-T

Variant names:

• chr1-175074831-C-T
• rs16847787
• NM_022093.2:c.-35-2553C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 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.-35-2553C>T		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.-35-2553C>T		intron	N/A	ENSP00000239462.4

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

African (AFR) AF: 0.166 AC: 6910 AN: 41526

American (AMR) AF: 0.0168 AC: 257 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 68012

Other (OTH) AF: 0.0265 AC: 56 AN: 2116

Alfa AF: 0.0416 Hom.: 51

Bravo AF: 0.0542

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.64
PhyloP100		-2.9
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: rs16847787; hg19: chr1-175043967;