rs8028808

Positions:

• chr15-77675074-G-A
• chr15-77675074-G-C

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-13+2015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,022 control chromosomes in the GnomAD database, including 5,046 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 0.22 (5046 hom., cov: 32)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-13+2015C>T		intron_variant			NP_001288115.1
LINGO1	NM_001301187.2	c.-13+2015C>T		intron_variant			NP_001288116.1
LINGO1	NM_001301189.2	c.-13+2015C>T		intron_variant			NP_001288118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000561030.5	c.-13+2015C>T		intron_variant		1		ENSP00000453853	P4
LINGO1	ENST00000559893.5	c.-13+2015C>T		intron_variant		4		ENSP00000454051
LINGO1	ENST00000561686.5	c.-13+15646C>T		intron_variant		3		ENSP00000455605

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34029 AN: 151904 Hom.: 5033 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.224 AC: 34080 AN: 152022 Hom.: 5046 Cov.: 32 AF XY: 0.222 AC XY: 16510 AN XY: 74316

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.222

Alfa AF: 0.162 Hom.: 1468

Bravo AF: 0.233

Asia WGS AF: 0.250 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8028808; hg19: chr15-77967416;