9-115038138-T-A

Variant names:

• chr9-115038138-T-A
• rs2274751
• NM_002160.4:c.5512+123A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002160.4(TNC):​c.5512+123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,358,710 control chromosomes in the GnomAD database, including 7,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (688 hom., cov: 33)
  • Exomes 𝑓: 0.099 (6380 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.384
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-115038138-T-A is Benign according to our data. Variant chr9-115038138-T-A is described in ClinVar as Benign. ClinVar VariationId is 1274867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 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.5512+123A>T		intron	N/A	NP_002151.2
	TNC	NM_001439065.1		c.6061+123A>T		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.6061+123A>T		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.5512+123A>T		intron	N/A	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.4693+123A>T		intron	N/A	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.4423+123A>T		intron	N/A	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13785 AN: 152160 Hom.: 688 Cov.: 33

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0985 AC: 118872 AN: 1206432 Hom.: 6380 AF XY: 0.0983 AC XY: 58267 AN XY: 592770

African (AFR) AF: 0.0554 AC: 1517 AN: 27392

American (AMR) AF: 0.0864 AC: 2603 AN: 30128

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2044 AN: 18718

East Asian (EAS) AF: 0.0843 AC: 3043 AN: 36090

South Asian (SAS) AF: 0.0523 AC: 3134 AN: 59878

European-Finnish (FIN) AF: 0.0821 AC: 3434 AN: 41824

Middle Eastern (MID) AF: 0.159 AC: 788 AN: 4956

European-Non Finnish (NFE) AF: 0.104 AC: 97459 AN: 936830

Other (OTH) AF: 0.0958 AC: 4850 AN: 50616

GnomAD4 genome AF: 0.0905 AC: 13786 AN: 152278 Hom.: 688 Cov.: 33 AF XY: 0.0892 AC XY: 6640 AN XY: 74452

African (AFR) AF: 0.0589 AC: 2447 AN: 41562

American (AMR) AF: 0.113 AC: 1726 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.0635 AC: 329 AN: 5184

South Asian (SAS) AF: 0.0480 AC: 231 AN: 4814

European-Finnish (FIN) AF: 0.0813 AC: 862 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7417 AN: 68020

Other (OTH) AF: 0.120 AC: 253 AN: 2116

Alfa AF: 0.0897 Hom.: 86

Bravo AF: 0.0947

Asia WGS AF: 0.0540 AC: 189 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Dec 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.38
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: rs2274751; hg19: chr9-117800417; COSMIC: COSV60792841; COSMIC: COSV60792841;