rs11856808

chr15-77680428-C-T

Variant summary

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

The ENST00000561030.5(LINGO1):c.-98-3254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,104 control chromosomes in the GnomAD database, including 14,520 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 0.42 (14520 hom., cov: 33)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_001301186.2	c.-98-3254G>A		intron_variant
LINGO1	NM_001301187.2	c.-98-3254G>A		intron_variant
LINGO1	NM_001301189.2	c.-98-3254G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000561030.5	c.-98-3254G>A		intron_variant		1		P4
LINGO1	ENST00000559893.5	c.-98-3254G>A		intron_variant		4
LINGO1	ENST00000561686.5	c.-13+10292G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63774 AN: 151986 Hom.: 14501 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.420 AC: 63843 AN: 152104 Hom.: 14520 Cov.: 33 AF XY: 0.421 AC XY: 31288 AN XY: 74352

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.419

Alfa AF: 0.358 Hom.: 13420

Bravo AF: 0.429

Asia WGS AF: 0.408 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.042
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11856808; hg19: chr15-77972770;