rs290018

Variant names:

• chr2-77403354-G-A
• rs290018
• NM_001134745.3:c.1551+114964C>T

Variant summary

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

The NM_001134745.3(LRRTM4):​c.1551+114964C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,548 control chromosomes in the GnomAD database, including 16,505 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 0.46 (16505 hom., cov: 31)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 2 publications found

Genes affected

LRRTM4 (HGNC:19411): (leucine rich repeat transmembrane neuronal 4) Predicted to enable heparan sulfate proteoglycan binding activity. Predicted to be involved in regulation of synapse assembly. Predicted to act upstream of or within AMPA glutamate receptor clustering; positive regulation of synapse assembly; and regulation of presynaptic membrane organization. Predicted to be located in postsynaptic membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in extracellular matrix; extracellular space; and glutamatergic synapse. Predicted to be integral component of postsynaptic density membrane. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1551+114964C>T		intron_variant	Intron 3 of 3	ENST00000409884.6	NP_001128217.1
LRRTM4	NM_001330370.2	c.1554+114964C>T		intron_variant	Intron 2 of 2		NP_001317299.1
LRRTM4	NM_001282924.3	c.1551+114964C>T		intron_variant	Intron 3 of 3		NP_001269853.1
LRRTM4	NR_146416.2	n.268+118755C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1551+114964C>T		intron_variant	Intron 3 of 3	1	NM_001134745.3	ENSP00000387297.1
LRRTM4	ENST00000409911.5	c.1554+114964C>T		intron_variant	Intron 2 of 2	5		ENSP00000387228.1
LRRTM4	ENST00000409093.1	c.1551+114964C>T		intron_variant	Intron 3 of 3	2		ENSP00000386357.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70230 AN: 151430 Hom.: 16481 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.464 AC: 70305 AN: 151548 Hom.: 16505 Cov.: 31 AF XY: 0.466 AC XY: 34462 AN XY: 74012

African (AFR) AF: 0.484 AC: 19977 AN: 41306

American (AMR) AF: 0.405 AC: 6150 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1639 AN: 3466

East Asian (EAS) AF: 0.603 AC: 3093 AN: 5128

South Asian (SAS) AF: 0.429 AC: 2063 AN: 4812

European-Finnish (FIN) AF: 0.485 AC: 5088 AN: 10480

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30649 AN: 67862

Other (OTH) AF: 0.447 AC: 944 AN: 2110

Alfa AF: 0.453 Hom.: 8143

Bravo AF: 0.460

Asia WGS AF: 0.522 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.088
DANN	Benign	0.14
PhyloP100		-1.2
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: rs290018; hg19: chr2-77630480;