rs6749190

Variant names:

• chr2-77442724-C-A
• rs6749190
• NM_001134745.3:c.1551+75594G>T

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+75594G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 152,202 control chromosomes in the GnomAD database, including 327 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 0.062 (327 hom., cov: 33)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 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.1551+75594G>T		intron	N/A	NP_001128217.1
	LRRTM4	NM_001330370.2		c.1554+75594G>T		intron	N/A	NP_001317299.1
	LRRTM4	NM_001282924.3		c.1551+75594G>T		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.1551+75594G>T		intron	N/A	ENSP00000387297.1
	LRRTM4	ENST00000409911.5	TSL:5	c.1554+75594G>T		intron	N/A	ENSP00000387228.1
	LRRTM4	ENST00000409093.1	TSL:2	c.1551+75594G>T		intron	N/A	ENSP00000386357.1

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9443 AN: 152086 Hom.: 321 Cov.: 33

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0777

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

GnomAD4 genome AF: 0.0622 AC: 9469 AN: 152202 Hom.: 327 Cov.: 33 AF XY: 0.0622 AC XY: 4630 AN XY: 74424

African (AFR) AF: 0.0720 AC: 2992 AN: 41536

American (AMR) AF: 0.0544 AC: 832 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5182

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4832

European-Finnish (FIN) AF: 0.0735 AC: 779 AN: 10594

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0615 AC: 4183 AN: 67992

Other (OTH) AF: 0.0859 AC: 181 AN: 2106

Alfa AF: 0.0628 Hom.: 800

Bravo AF: 0.0626

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.26
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: rs6749190; hg19: chr2-77669850;