chr15-77663174-C-T

Variant names:

• chr15-77663174-C-T
• rs8030859
• ENST00000561030.5:c.-13+13915G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561030.5(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 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 3 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-AS2 (HGNC:51423): (LINGO1 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-13+13915G>A		intron_variant	Intron 5 of 5		NP_001288115.1
LINGO1	NM_001301187.2	c.-13+13915G>A		intron_variant	Intron 5 of 5		NP_001288116.1
LINGO1	NM_001301189.2	c.-13+13915G>A		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.-13+13915G>A		intron_variant	Intron 3 of 3	1		ENSP00000453853.1
LINGO1-AS2	ENST00000557799.2	n.140+2991C>T		intron_variant	Intron 1 of 2	1
LINGO1	ENST00000561686.5	c.-13+27546G>A		intron_variant	Intron 3 of 3	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

African (AFR) AF: 0.503 AC: 20834 AN: 41454

American (AMR) AF: 0.184 AC: 2813 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3470

East Asian (EAS) AF: 0.109 AC: 565 AN: 5180

South Asian (SAS) AF: 0.134 AC: 643 AN: 4810

European-Finnish (FIN) AF: 0.204 AC: 2163 AN: 10604

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16028 AN: 67988

Other (OTH) AF: 0.275 AC: 580 AN: 2106

Alfa AF: 0.265 Hom.: 1376

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
PhyloP100		-0.63
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: rs8030859; hg19: chr15-77955516;