rs8030859

Positions:

• chr15-77663174-C-T

Variant summary

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

The NM_001301186.2(LINGO1):​c.-13+13915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,122 control chromosomes in the GnomAD database, including 8,024 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 0.29 (8024 hom., cov: 33)
• Consequence: LINGO1 NM_001301186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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]

LINGO1-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-13+13915G>A		intron_variant			NP_001288115.1
LINGO1	NM_001301187.2	c.-13+13915G>A		intron_variant			NP_001288116.1
LINGO1	NM_001301189.2	c.-13+13915G>A		intron_variant			NP_001288118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000561030.5	c.-13+13915G>A		intron_variant		1		ENSP00000453853.1
LINGO1-AS2	ENST00000557799.1	n.132+2991C>T		intron_variant		1
LINGO1	ENST00000561686.5	c.-13+27546G>A		intron_variant		3		ENSP00000455605.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44547 AN: 152004 Hom.: 8022 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.293 AC: 44580 AN: 152122 Hom.: 8024 Cov.: 33 AF XY: 0.288 AC XY: 21389 AN XY: 74366

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.275

Alfa AF: 0.249 Hom.: 1049

Bravo AF: 0.301

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.58
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8030859; hg19: chr15-77955516;