rs17752074

Positions:

• chr2-77523463-G-A

Variant summary

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

The ENST00000456154.1(LRRTM4):​c.-29-3599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 152,074 control chromosomes in the GnomAD database, including 241 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 0.053 (241 hom., cov: 32)
• Consequence: LRRTM4 ENST00000456154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.77523463G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000456154.1	c.-29-3599C>T		intron_variant		4		ENSP00000408722.1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8098 AN: 151956 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0534 AC: 8119 AN: 152074 Hom.: 241 Cov.: 32 AF XY: 0.0524 AC XY: 3892 AN XY: 74342

Gnomad4 AFR AF: 0.0555

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0669

Gnomad4 EAS AF: 0.0103

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0607

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0578 Hom.: 120

Bravo AF: 0.0514

Asia WGS AF: 0.0350 AC: 123 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17752074; hg19: chr2-77750589;