chr2-76794802-C-T

Variant names:

• chr2-76794802-C-T
• rs10170138
• NM_001134745.3:c.1552-45886G>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.1552-45886G>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 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134745.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRTM4	NM_001134745.3	MANE Select	c.1552-45886G>A		intron	N/A	NP_001128217.1
	LRRTM4	NM_001330370.2		c.1555-45886G>A		intron	N/A	NP_001317299.1
	LRRTM4	NM_001282924.3		c.1552-45886G>A		intron	N/A	NP_001269853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRTM4	ENST00000409884.6	TSL:1 MANE Select	c.1552-45886G>A		intron	N/A	ENSP00000387297.1
	LRRTM4	ENST00000409911.5	TSL:5	c.1555-45886G>A		intron	N/A	ENSP00000387228.1
	LRRTM4	ENST00000409093.1	TSL:2	c.1552-45886G>A		intron	N/A	ENSP00000386357.1

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

African (AFR) AF: 0.204 AC: 8434 AN: 41416

American (AMR) AF: 0.107 AC: 1629 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3466

East Asian (EAS) AF: 0.108 AC: 559 AN: 5166

South Asian (SAS) AF: 0.0964 AC: 464 AN: 4812

European-Finnish (FIN) AF: 0.174 AC: 1837 AN: 10542

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9863 AN: 67778

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.148 Hom.: 7309

Bravo AF: 0.153

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.39
DANN	Benign	0.28
PhyloP100		-0.54
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: rs10170138; hg19: chr2-77021928;