rs13329256

Positions:

• chr15-77633918-T-A
• chr15-77633918-T-G

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-12-18018A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,150 control chromosomes in the GnomAD database, including 3,732 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 0.16 (3732 hom., cov: 32)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_001301186.2	c.-12-18018A>T		intron_variant
LINGO1	NM_001301187.2	c.-12-18018A>T		intron_variant
LINGO1	NM_001301189.2	c.-12-18018A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000561030.5	c.-12-18018A>T		intron_variant		1		P4
LINGO1	ENST00000557798.1	c.21+358A>T		intron_variant		3
LINGO1	ENST00000559893.5	c.-12-18018A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24010 AN: 152030 Hom.: 3710 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.158 AC: 24078 AN: 152150 Hom.: 3732 Cov.: 32 AF XY: 0.157 AC XY: 11650 AN XY: 74404

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0406 Hom.: 73

Bravo AF: 0.170

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.7
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13329256; hg19: chr15-77926260;