rs13329256

Variant names:

• chr15-77633918-T-A
• rs13329256
• ENST00000561030.5:c.-12-18018A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 64

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-12-18018A>T		intron_variant	Intron 5 of 5		NP_001288115.1
LINGO1	NM_001301187.2	c.-12-18018A>T		intron_variant	Intron 5 of 5		NP_001288116.1
LINGO1	NM_001301189.2	c.-12-18018A>T		intron_variant	Intron 5 of 5		NP_001288118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000561030.5	c.-12-18018A>T		intron_variant	Intron 3 of 3	1		ENSP00000453853.1
LINGO1	ENST00000557798.1	c.21+358A>T		intron_variant	Intron 1 of 1	3		ENSP00000453780.1
LINGO1	ENST00000561686.5	c.-12-18018A>T		intron_variant	Intron 3 of 3	3		ENSP00000455605.1

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

African (AFR) AF: 0.406 AC: 16848 AN: 41462

American (AMR) AF: 0.0733 AC: 1121 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.129 AC: 668 AN: 5182

South Asian (SAS) AF: 0.109 AC: 525 AN: 4818

European-Finnish (FIN) AF: 0.0533 AC: 565 AN: 10608

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0537 AC: 3655 AN: 68004

Other (OTH) AF: 0.146 AC: 309 AN: 2112

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
PhyloP100		-0.83
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13329256; hg19: chr15-77926260;