2-77436138-C-T

Position:

• chr2-77436138-C-T

Variant summary

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

The NM_001134745.3(LRRTM4):​c.1551+82180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,894 control chromosomes in the GnomAD database, including 25,483 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 0.58 (25483 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1551+82180G>A		intron_variant		ENST00000409884.6	NP_001128217.1
LRRTM4	NM_001282924.3	c.1551+82180G>A		intron_variant			NP_001269853.1
LRRTM4	NM_001330370.2	c.1554+82180G>A		intron_variant			NP_001317299.1
LRRTM4	NR_146416.2	n.268+85971G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1551+82180G>A		intron_variant		1	NM_001134745.3	ENSP00000387297	P4
LRRTM4	ENST00000409093.1	c.1551+82180G>A		intron_variant		2		ENSP00000386357	P4
LRRTM4	ENST00000409911.5	c.1554+82180G>A		intron_variant		5		ENSP00000387228	A1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87352 AN: 151776 Hom.: 25443 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.576 AC: 87450 AN: 151894 Hom.: 25483 Cov.: 32 AF XY: 0.576 AC XY: 42796 AN XY: 74254

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.550

Alfa AF: 0.540 Hom.: 44389

Bravo AF: 0.572

Asia WGS AF: 0.499 AC: 1733 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.24

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: rs1922807; hg19: chr2-77663264;