rs17752074

Variant names:

• chr2-77523463-G-A
• rs17752074
• ENST00000456154.1:c.-29-3599C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456154.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRTM4	ENST00000456154.1	TSL:4	c.-29-3599C>T		intron	N/A	ENSP00000408722.1	C9JM64

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

African (AFR) AF: 0.0555 AC: 2302 AN: 41508

American (AMR) AF: 0.0376 AC: 573 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0669 AC: 232 AN: 3470

East Asian (EAS) AF: 0.0103 AC: 53 AN: 5142

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4822

European-Finnish (FIN) AF: 0.0563 AC: 597 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0607 AC: 4124 AN: 67956

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0571 Hom.: 136

Bravo AF: 0.0514

Asia WGS AF: 0.0350 AC: 123 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.53
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs17752074; hg19: chr2-77750589;