2-77019205-A-G

Variant names:

• chr2-77019205-A-G
• rs6547115
• NM_001134745.3:c.1552-270289T>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.1552-270289T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 145,836 control chromosomes in the GnomAD database, including 24,439 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 0.55 (24439 hom., cov: 22)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 9 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM4	NM_001134745.3	c.1552-270289T>C		intron_variant	Intron 3 of 3	ENST00000409884.6	NP_001128217.1
LRRTM4	NM_001330370.2	c.1555-270289T>C		intron_variant	Intron 2 of 2		NP_001317299.1
LRRTM4	NM_001282924.3	c.1552-270289T>C		intron_variant	Intron 3 of 3		NP_001269853.1
LRRTM4	NR_146416.2	n.269-270289T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-270289T>C		intron_variant	Intron 3 of 3	1	NM_001134745.3	ENSP00000387297.1
LRRTM4	ENST00000409911.5	c.1555-270289T>C		intron_variant	Intron 2 of 2	5		ENSP00000387228.1
LRRTM4	ENST00000409093.1	c.1552-270289T>C		intron_variant	Intron 3 of 3	2		ENSP00000386357.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 80511 AN: 145740 Hom.: 24388 Cov.: 22

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.457

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.553 AC: 80605 AN: 145836 Hom.: 24439 Cov.: 22 AF XY: 0.554 AC XY: 39200 AN XY: 70724

African (AFR) AF: 0.810 AC: 31635 AN: 39036

American (AMR) AF: 0.556 AC: 8024 AN: 14430

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1627 AN: 3452

East Asian (EAS) AF: 0.665 AC: 3257 AN: 4898

South Asian (SAS) AF: 0.506 AC: 2349 AN: 4640

European-Finnish (FIN) AF: 0.485 AC: 4503 AN: 9290

Middle Eastern (MID) AF: 0.451 AC: 128 AN: 284

European-Non Finnish (NFE) AF: 0.412 AC: 27573 AN: 66880

Other (OTH) AF: 0.524 AC: 1066 AN: 2034

Alfa AF: 0.492 Hom.: 27614

Bravo AF: 0.578

Asia WGS AF: 0.629 AC: 2180 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.88
PhyloP100		-1.0
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: rs6547115; hg19: chr2-77246331;