chr2-76995684-A-C

Variant names:

• chr2-76995684-A-C
• rs1470504
• NM_001134745.3:c.1552-246768T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134745.3(LRRTM4):​c.1552-246768T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,832 control chromosomes in the GnomAD database, including 19,998 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 0.50 (19998 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72
• Publications: 8 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]

LRRTM4-AS1 (HGNC:40889): (LRRTM4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 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.1552-246768T>G		intron	N/A	NP_001128217.1
	LRRTM4	NM_001330370.2		c.1555-246768T>G		intron	N/A	NP_001317299.1
	LRRTM4	NM_001282924.3		c.1552-246768T>G		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.1552-246768T>G		intron	N/A	ENSP00000387297.1
	LRRTM4-AS1	ENST00000445178.1	TSL:1	n.232+5758A>C		intron	N/A
	LRRTM4	ENST00000409911.5	TSL:5	c.1555-246768T>G		intron	N/A	ENSP00000387228.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76414 AN: 151714 Hom.: 19955 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.504 AC: 76520 AN: 151832 Hom.: 19998 Cov.: 32 AF XY: 0.506 AC XY: 37510 AN XY: 74190

African (AFR) AF: 0.635 AC: 26293 AN: 41420

American (AMR) AF: 0.531 AC: 8075 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3468

East Asian (EAS) AF: 0.608 AC: 3124 AN: 5136

South Asian (SAS) AF: 0.486 AC: 2340 AN: 4816

European-Finnish (FIN) AF: 0.484 AC: 5109 AN: 10558

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28370 AN: 67916

Other (OTH) AF: 0.489 AC: 1030 AN: 2106

Alfa AF: 0.447 Hom.: 40025

Bravo AF: 0.513

Asia WGS AF: 0.578 AC: 2007 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0050
DANN	Benign	0.53
PhyloP100		-2.7
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: rs1470504; hg19: chr2-77222810;