rs10170138

Positions:

• chr2-76794802-C-T

Variant summary

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

The ENST00000409884.6(LRRTM4):​c.1552-45886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,772 control chromosomes in the GnomAD database, including 2,037 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 0.16 (2037 hom., cov: 32)
• Consequence: LRRTM4 ENST00000409884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1552-45886G>A		intron_variant		ENST00000409884.6	NP_001128217.1
LRRTM4	NM_001282924.3	c.1552-45886G>A		intron_variant			NP_001269853.1
LRRTM4	NM_001330370.2	c.1555-45886G>A		intron_variant			NP_001317299.1
LRRTM4	NR_146416.2	n.269-45886G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-45886G>A		intron_variant		1	NM_001134745.3	ENSP00000387297	P4
LRRTM4	ENST00000409093.1	c.1552-45886G>A		intron_variant		2		ENSP00000386357	P4
LRRTM4	ENST00000409911.5	c.1555-45886G>A		intron_variant		5		ENSP00000387228	A1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23858 AN: 151652 Hom.: 2031 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.157 AC: 23883 AN: 151772 Hom.: 2037 Cov.: 32 AF XY: 0.157 AC XY: 11658 AN XY: 74162

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0964

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.155

Alfa AF: 0.144 Hom.: 3326

Bravo AF: 0.153

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.39
DANN	Benign	0.28

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: rs10170138; hg19: chr2-77021928;