rs6547110

chr2-76987772-T-Achr2-76987772-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134745.3(LRRTM4):c.1552-238856A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,460 control chromosomes in the GnomAD database, including 26,671 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 0.57 (26671 hom., cov: 31)
• Consequence: LRRTM4 NM_001134745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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]

LRRTM4-AS1 (HGNC:40889): (LRRTM4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRTM4	NM_001134745.3	c.1552-238856A>T		intron_variant		ENST00000409884.6
LRRTM4-AS1	NR_110284.1	n.126+278T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM4	ENST00000409884.6	c.1552-238856A>T		intron_variant		1	NM_001134745.3	P4
LRRTM4-AS1	ENST00000445178.1	n.126+278T>A		intron_variant, non_coding_transcript_variant		1
LRRTM4	ENST00000409093.1	c.1552-238856A>T		intron_variant		2		P4
LRRTM4	ENST00000409911.5	c.1555-238856A>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86241 AN: 151340 Hom.: 26614 Cov.: 31

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.570 AC: 86359 AN: 151460 Hom.: 26671 Cov.: 31 AF XY: 0.574 AC XY: 42425 AN XY: 73962

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.538

Alfa AF: 0.511 Hom.: 2650

Bravo AF: 0.589

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.6
Dann	Benign	0.45

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: rs6547110; hg19: chr2-77214898;