rs2860941

chr2-77074057-C-Gchr2-77074057-C-T

Variant summary

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

The NM_001134745.3(LRRTM4):c.1552-325141G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 150,722 control chromosomes in the GnomAD database, including 14,285 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 0.40 (14285 hom., cov: 33)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRTM4	NM_001134745.3	c.1552-325141G>C		intron_variant		ENST00000409884.6
LRRTM4	NM_001282924.3	c.1552-325141G>C		intron_variant
LRRTM4	NM_001330370.2	c.1555-325141G>C		intron_variant
LRRTM4	NR_146416.2	n.269-325141G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-325141G>C		intron_variant		1	NM_001134745.3	P4
LRRTM4	ENST00000409093.1	c.1552-325141G>C		intron_variant		2		P4
LRRTM4	ENST00000409911.5	c.1555-325141G>C		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 60803 AN: 150606 Hom.: 14237 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.404 AC: 60913 AN: 150722 Hom.: 14285 Cov.: 33 AF XY: 0.408 AC XY: 30059 AN XY: 73696

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.400

Alfa AF: 0.157 Hom.: 255

Bravo AF: 0.419

Asia WGS AF: 0.580 AC: 2010 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.6
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2860941; hg19: chr2-77301183;