2-76995684-A-C

Position:

• chr2-76995684-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1552-246768T>G		intron_variant		ENST00000409884.6	NP_001128217.1
LRRTM4-AS1	NR_110284.1	n.232+5758A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-246768T>G		intron_variant		1	NM_001134745.3	ENSP00000387297	P4
LRRTM4-AS1	ENST00000445178.1	n.232+5758A>C		intron_variant, non_coding_transcript_variant		1
LRRTM4	ENST00000409093.1	c.1552-246768T>G		intron_variant		2		ENSP00000386357	P4
LRRTM4	ENST00000409911.5	c.1555-246768T>G		intron_variant		5		ENSP00000387228	A1

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

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.489

Alfa AF: 0.424 Hom.: 20537

Bravo AF: 0.513

Asia WGS AF: 0.578 AC: 2007 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0050
DANN	Benign	0.53

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: rs1470504; hg19: chr2-77222810;