rs35974940

Variant names:

• chr11-131375192-G-T
• rs35974940
• NM_001352005.2:c.82+4304G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001352005.2(NTM):​c.82+4304G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,102 control chromosomes in the GnomAD database, including 98 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 0.033 (98 hom., cov: 33)
• Consequence: NTM NM_001352005.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0327 (4981/152102) while in subpopulation NFE AF = 0.0377 (2562/67994). AF 95% confidence interval is 0.0365. There are 98 homozygotes in GnomAd4. There are 2353 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 98 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTM	NM_001352005.2	c.82+4304G>T		intron_variant	Intron 1 of 8	ENST00000683400.1	NP_001338934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTM	ENST00000683400.1	c.82+4304G>T		intron_variant	Intron 1 of 8		NM_001352005.2	ENSP00000507313.1
NTM	ENST00000374791.7	c.82+4304G>T		intron_variant	Intron 1 of 7	1		ENSP00000363923.3
NTM	ENST00000436745.5	c.-66+4304G>T		intron_variant	Intron 1 of 2	3		ENSP00000409221.1
NTM	ENST00000477098.1	n.260+4304G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4979 AN: 151984 Hom.: 98 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0327 AC: 4981 AN: 152102 Hom.: 98 Cov.: 33 AF XY: 0.0316 AC XY: 2353 AN XY: 74352

African (AFR) AF: 0.0268 AC: 1114 AN: 41498

American (AMR) AF: 0.0256 AC: 391 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.0231 AC: 119 AN: 5146

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4808

European-Finnish (FIN) AF: 0.0382 AC: 405 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2562 AN: 67994

Other (OTH) AF: 0.0341 AC: 72 AN: 2112

Alfa AF: 0.0361 Hom.: 140

Bravo AF: 0.0333

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.66
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35974940; hg19: chr11-131245087;