15-77691460-T-C

Position:

• chr15-77691460-T-C

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-280-559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,776 control chromosomes in the GnomAD database, including 24,643 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 (24643 hom., cov: 31)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

LINGO1 (HGNC:21205): (leucine rich repeat and Ig domain containing 1) Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within generation of neurons and protein kinase B signaling. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. Implicated in autosomal recessive non-syndromic intellectual disability and glaucoma. [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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_001301186.2	c.-280-559A>G		intron_variant
LINGO1	NM_001301187.2	c.-280-559A>G		intron_variant
LINGO1	NM_001301189.2	c.-280-559A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000561030.5	c.-280-559A>G		intron_variant		1		P4
LINGO1	ENST00000559893.5	c.-280-559A>G		intron_variant		4
LINGO1	ENST00000561686.5	c.-194-559A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85862 AN: 151658 Hom.: 24621 Cov.: 31

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.566 AC: 85942 AN: 151776 Hom.: 24643 Cov.: 31 AF XY: 0.564 AC XY: 41841 AN XY: 74172

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.581

Alfa AF: 0.547 Hom.: 32042

Bravo AF: 0.573

Asia WGS AF: 0.524 AC: 1824 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12898861; hg19: chr15-77983802;