rs1470506

Variant names:

• chr2-76996812-C-T
• rs1470506
• NM_001134745.3:c.1552-247896G>A

Variant summary

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

The NM_001134745.3(LRRTM4):​c.1552-247896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,744 control chromosomes in the GnomAD database, including 19,919 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 0.50 (19919 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 6 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]

LRRTM4-AS1 (HGNC:40889): (LRRTM4 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1552-247896G>A		intron_variant	Intron 3 of 3	ENST00000409884.6	NP_001128217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-247896G>A		intron_variant	Intron 3 of 3	1	NM_001134745.3	ENSP00000387297.1
LRRTM4-AS1	ENST00000445178.1	n.232+6886C>T		intron_variant	Intron 3 of 3	1
LRRTM4	ENST00000409911.5	c.1555-247896G>A		intron_variant	Intron 2 of 2	5		ENSP00000387228.1
LRRTM4	ENST00000409093.1	c.1552-247896G>A		intron_variant	Intron 3 of 3	2		ENSP00000386357.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76296 AN: 151626 Hom.: 19876 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.503 AC: 76402 AN: 151744 Hom.: 19919 Cov.: 32 AF XY: 0.505 AC XY: 37454 AN XY: 74128

African (AFR) AF: 0.634 AC: 26268 AN: 41404

American (AMR) AF: 0.529 AC: 8050 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3466

East Asian (EAS) AF: 0.609 AC: 3115 AN: 5114

South Asian (SAS) AF: 0.486 AC: 2339 AN: 4812

European-Finnish (FIN) AF: 0.484 AC: 5094 AN: 10516

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28335 AN: 67892

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.524 Hom.: 8043

Bravo AF: 0.512

Asia WGS AF: 0.577 AC: 2004 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		0.15
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: rs1470506; hg19: chr2-77223938;