chr2-76810883-A-C

Variant names:

• chr2-76810883-A-C
• rs977744
• NM_001134745.3:c.1552-61967T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134745.3(LRRTM4):​c.1552-61967T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,974 control chromosomes in the GnomAD database, including 15,044 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 0.43 (15044 hom., cov: 32)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1552-61967T>G		intron_variant	Intron 3 of 3	ENST00000409884.6	NP_001128217.1
LRRTM4	NM_001330370.2	c.1555-61967T>G		intron_variant	Intron 2 of 2		NP_001317299.1
LRRTM4	NM_001282924.3	c.1552-61967T>G		intron_variant	Intron 3 of 3		NP_001269853.1
LRRTM4	NR_146416.2	n.269-61967T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-61967T>G		intron_variant	Intron 3 of 3	1	NM_001134745.3	ENSP00000387297.1
LRRTM4	ENST00000409911.5	c.1555-61967T>G		intron_variant	Intron 2 of 2	5		ENSP00000387228.1
LRRTM4	ENST00000409093.1	c.1552-61967T>G		intron_variant	Intron 3 of 3	2		ENSP00000386357.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65431 AN: 151856 Hom.: 15011 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.431 AC: 65515 AN: 151974 Hom.: 15044 Cov.: 32 AF XY: 0.437 AC XY: 32447 AN XY: 74272

African (AFR) AF: 0.477 AC: 19757 AN: 41434

American (AMR) AF: 0.550 AC: 8385 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3466

East Asian (EAS) AF: 0.759 AC: 3924 AN: 5172

South Asian (SAS) AF: 0.538 AC: 2590 AN: 4818

European-Finnish (FIN) AF: 0.375 AC: 3959 AN: 10558

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.349 AC: 23746 AN: 67958

Other (OTH) AF: 0.451 AC: 953 AN: 2112

Alfa AF: 0.337 Hom.: 1707

Bravo AF: 0.450

Asia WGS AF: 0.692 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.26
DANN	Benign	0.53
PhyloP100		-2.0
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: rs977744; hg19: chr2-77038009;