rs977744

chr2-76810883-A-Cchr2-76810883-A-T

Variant summary

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

The NM_001134745.3(LRRTM4):c.1552-61967T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,974 control chromosomes in the GnomAD database, including 15,044 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 0.43 (15044 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRTM4	NM_001134745.3	c.1552-61967T>G		intron_variant		ENST00000409884.6
LRRTM4	NM_001282924.3	c.1552-61967T>G		intron_variant
LRRTM4	NM_001330370.2	c.1555-61967T>G		intron_variant
LRRTM4	NR_146416.2	n.269-61967T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-61967T>G		intron_variant		1	NM_001134745.3	P4
LRRTM4	ENST00000409093.1	c.1552-61967T>G		intron_variant		2		P4
LRRTM4	ENST00000409911.5	c.1555-61967T>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65431 AN: 151856 Hom.: 15011 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.431 AC: 65515 AN: 151974 Hom.: 15044 Cov.: 32 AF XY: 0.437 AC XY: 32447 AN XY: 74272

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.451

Alfa AF: 0.333 Hom.: 1628

Bravo AF: 0.450

Asia WGS AF: 0.692 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.26
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: rs977744; hg19: chr2-77038009;