rs1556220

Variant names:

• chr9-115050498-T-C
• rs1556220
• NM_002160.4:c.4580-1966A>G

Variant summary

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

The NM_002160.4(TNC):​c.4580-1966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 152,228 control chromosomes in the GnomAD database, including 379 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 0.060 (379 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 2 publications found

Genes affected

TNC (HGNC:5318): (tenascin C) This gene encodes an extracellular matrix protein with a spatially and temporally restricted tissue distribution. This protein is homohexameric with disulfide-linked subunits, and contains multiple EGF-like and fibronectin type-III domains. It is implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity, and neuronal regeneration. [provided by RefSeq, Jul 2011]

DELEC1 (HGNC:23658): (deleted in esophageal cancer 1) The function of this gene is not known. This gene is located in a region commonly deleted in esophageal squamous cell carcinomas. Gene expression is reduced or absent in these carcinomas and thus this is a candidate tumor suppressor gene for esophageal squamous cell carcinomas. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002160.4. 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
	TNC	NM_002160.4	MANE Select	c.4580-1966A>G		intron	N/A	NP_002151.2
	TNC	NM_001439065.1		c.5129-1966A>G		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.5129-1966A>G		intron	N/A	NP_001425995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.4580-1966A>G		intron	N/A	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.4307-8157A>G		intron	N/A	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.3763+2242A>G		intron	N/A	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9087 AN: 152110 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0627

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

GnomAD4 genome AF: 0.0598 AC: 9109 AN: 152228 Hom.: 379 Cov.: 32 AF XY: 0.0610 AC XY: 4542 AN XY: 74436

African (AFR) AF: 0.0914 AC: 3795 AN: 41530

American (AMR) AF: 0.0966 AC: 1478 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.113 AC: 585 AN: 5178

South Asian (SAS) AF: 0.0232 AC: 112 AN: 4822

European-Finnish (FIN) AF: 0.0755 AC: 800 AN: 10598

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0298 AC: 2026 AN: 68012

Other (OTH) AF: 0.0654 AC: 138 AN: 2110

Alfa AF: 0.0402 Hom.: 313

Bravo AF: 0.0643

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1556220; hg19: chr9-117812777;