2-77436138-C-T

Variant names:

• chr2-77436138-C-T
• rs1922807
• NM_001134745.3:c.1551+82180G>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.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
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRTM4	NM_001134745.3	MANE Select	c.1551+82180G>A		intron	N/A	NP_001128217.1	Q86VH4-1
	LRRTM4	NM_001330370.2		c.1554+82180G>A		intron	N/A	NP_001317299.1	B8ZZ84
	LRRTM4	NM_001282924.3		c.1551+82180G>A		intron	N/A	NP_001269853.1	Q86VH4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRTM4	ENST00000409884.6	TSL:1 MANE Select	c.1551+82180G>A		intron	N/A	ENSP00000387297.1	Q86VH4-1
	LRRTM4	ENST00000409911.5	TSL:5	c.1554+82180G>A		intron	N/A	ENSP00000387228.1	B8ZZ84
	LRRTM4	ENST00000409093.1	TSL:2	c.1551+82180G>A		intron	N/A	ENSP00000386357.1	Q86VH4-1

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

African (AFR) AF: 0.677 AC: 28041 AN: 41428

American (AMR) AF: 0.507 AC: 7728 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2306 AN: 5170

South Asian (SAS) AF: 0.533 AC: 2563 AN: 4812

European-Finnish (FIN) AF: 0.590 AC: 6235 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37158 AN: 67892

Other (OTH) AF: 0.550 AC: 1160 AN: 2110

Alfa AF: 0.548 Hom.: 95489

Bravo AF: 0.572

Asia WGS AF: 0.499 AC: 1733 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.24
PhyloP100		0.65
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: rs1922807; hg19: chr2-77663264;