2-76946110-G-A

Variant names:

• chr2-76946110-G-A
• rs10520173
• NM_001134745.3:c.1552-197194C>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.1552-197194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 151,854 control chromosomes in the GnomAD database, including 482 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 0.053 (482 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1552-197194C>T		intron_variant	Intron 3 of 3	ENST00000409884.6	NP_001128217.1
LRRTM4	NM_001330370.2	c.1555-197194C>T		intron_variant	Intron 2 of 2		NP_001317299.1
LRRTM4	NM_001282924.3	c.1552-197194C>T		intron_variant	Intron 3 of 3		NP_001269853.1
LRRTM4	NR_146416.2	n.269-197194C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-197194C>T		intron_variant	Intron 3 of 3	1	NM_001134745.3	ENSP00000387297.1
LRRTM4	ENST00000409911.5	c.1555-197194C>T		intron_variant	Intron 2 of 2	5		ENSP00000387228.1
LRRTM4	ENST00000409093.1	c.1552-197194C>T		intron_variant	Intron 3 of 3	2		ENSP00000386357.1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7982 AN: 151736 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00472

Gnomad OTH AF: 0.0403

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

GnomAD4 genome AF: 0.0526 AC: 7988 AN: 151854 Hom.: 482 Cov.: 32 AF XY: 0.0555 AC XY: 4120 AN XY: 74246

African (AFR) AF: 0.129 AC: 5357 AN: 41458

American (AMR) AF: 0.0652 AC: 995 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3468

East Asian (EAS) AF: 0.140 AC: 721 AN: 5160

South Asian (SAS) AF: 0.0387 AC: 186 AN: 4804

European-Finnish (FIN) AF: 0.0250 AC: 265 AN: 10580

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00472 AC: 320 AN: 67820

Other (OTH) AF: 0.0398 AC: 84 AN: 2108

Alfa AF: 0.00274 Hom.: 2

Bravo AF: 0.0616

Asia WGS AF: 0.0840 AC: 293 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		-0.11
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: rs10520173; hg19: chr2-77173236;