2-77467701-A-G

Variant names:

• chr2-77467701-A-G
• rs1922805
• NM_001134745.3:c.1551+50617T>C

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+50617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,144 control chromosomes in the GnomAD database, including 57,251 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 0.87 (57251 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.899 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+50617T>C		intron	N/A	NP_001128217.1	Q86VH4-1
	LRRTM4	NM_001330370.2		c.1554+50617T>C		intron	N/A	NP_001317299.1	B8ZZ84
	LRRTM4	NM_001282924.3		c.1551+50617T>C		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+50617T>C		intron	N/A	ENSP00000387297.1	Q86VH4-1
	LRRTM4	ENST00000409911.5	TSL:5	c.1554+50617T>C		intron	N/A	ENSP00000387228.1	B8ZZ84
	LRRTM4	ENST00000409093.1	TSL:2	c.1551+50617T>C		intron	N/A	ENSP00000386357.1	Q86VH4-1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131768 AN: 152026 Hom.: 57211 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.867 AC: 131864 AN: 152144 Hom.: 57251 Cov.: 32 AF XY: 0.869 AC XY: 64656 AN XY: 74390

African (AFR) AF: 0.815 AC: 33795 AN: 41466

American (AMR) AF: 0.903 AC: 13792 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3030 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4174 AN: 5156

South Asian (SAS) AF: 0.921 AC: 4448 AN: 4828

European-Finnish (FIN) AF: 0.922 AC: 9779 AN: 10610

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60043 AN: 68020

Other (OTH) AF: 0.856 AC: 1807 AN: 2112

Alfa AF: 0.871 Hom.: 80303

Bravo AF: 0.861

Asia WGS AF: 0.879 AC: 3057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.42
PhyloP100		0.0060
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: rs1922805; hg19: chr2-77694827;