rs2305272

Positions:

• chr11-132307669-C-T

Variant summary

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

The NM_001352005.2(NTM):​c.527-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,026 control chromosomes in the GnomAD database, including 27,045 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 0.16 (2260 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24785 hom.)
• Consequence: NTM NM_001352005.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

Genes affected

NTM (HGNC:17941): (neurotrimin) This gene encodes a member of the IgLON (LAMP, OBCAM, Ntm) family of immunoglobulin (Ig) domain-containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules. The encoded protein may promote neurite outgrowth and adhesion via a homophilic mechanism. This gene is closely linked to a related family member, opioid binding protein/cell adhesion molecule-like (OPCML), on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTM	NM_001352005.2	c.527-20C>T		intron_variant		ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.527-20C>T		intron_variant			NM_001352005.2	ENSP00000507313	A1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23711 AN: 152080 Hom.: 2263 Cov.: 33

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.193 AC: 48381 AN: 250434 Hom.: 5504 AF XY: 0.191 AC XY: 25815 AN XY: 135316

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.352

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.178 AC: 259874 AN: 1460828 Hom.: 24785 Cov.: 31 AF XY: 0.178 AC XY: 129546 AN XY: 726690

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.156 AC: 23710 AN: 152198 Hom.: 2260 Cov.: 33 AF XY: 0.159 AC XY: 11859 AN XY: 74424

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.186

Alfa AF: 0.185 Hom.: 2879

Bravo AF: 0.163

Asia WGS AF: 0.283 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.44

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: rs2305272; hg19: chr11-132177563; COSMIC: COSV66181103; COSMIC: COSV66181103;