2-77019205-A-G

Position:

• chr2-77019205-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LRRTM4	NM_001134745.3	c.1552-270289T>C		intron_variant		ENST00000409884.6
LRRTM4	NM_001282924.3	c.1552-270289T>C		intron_variant
LRRTM4	NM_001330370.2	c.1555-270289T>C		intron_variant
LRRTM4	NR_146416.2	n.269-270289T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-270289T>C		intron_variant		1	NM_001134745.3	P4
LRRTM4	ENST00000409093.1	c.1552-270289T>C		intron_variant		2		P4
LRRTM4	ENST00000409911.5	c.1555-270289T>C		intron_variant		5		A1

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

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.524

Alfa AF: 0.454 Hom.: 15709

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6547115; hg19: chr2-77246331;