2-76944940-C-T

Variant names:

• chr2-76944940-C-T
• rs1921626
• NM_001134745.3:c.1552-196024G>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.1552-196024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,056 control chromosomes in the GnomAD database, including 1,373 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 0.11 (1373 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1552-196024G>A		intron_variant	Intron 3 of 3	ENST00000409884.6	NP_001128217.1
LRRTM4	NM_001330370.2	c.1555-196024G>A		intron_variant	Intron 2 of 2		NP_001317299.1
LRRTM4	NM_001282924.3	c.1552-196024G>A		intron_variant	Intron 3 of 3		NP_001269853.1
LRRTM4	NR_146416.2	n.269-196024G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-196024G>A		intron_variant	Intron 3 of 3	1	NM_001134745.3	ENSP00000387297.1
LRRTM4	ENST00000409911.5	c.1555-196024G>A		intron_variant	Intron 2 of 2	5		ENSP00000387228.1
LRRTM4	ENST00000409093.1	c.1552-196024G>A		intron_variant	Intron 3 of 3	2		ENSP00000386357.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16734 AN: 151938 Hom.: 1364 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.110 AC: 16775 AN: 152056 Hom.: 1373 Cov.: 32 AF XY: 0.116 AC XY: 8606 AN XY: 74330

African (AFR) AF: 0.0753 AC: 3127 AN: 41524

American (AMR) AF: 0.157 AC: 2391 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3468

East Asian (EAS) AF: 0.462 AC: 2376 AN: 5142

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1375 AN: 10576

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.0813 AC: 5524 AN: 67940

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.0814 Hom.: 329

Bravo AF: 0.111

Asia WGS AF: 0.365 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.80
PhyloP100		-1.6
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: rs1921626; hg19: chr2-77172066;