rs7176315

chr15-77672569-A-G

Variant summary

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

The ENST00000561030.5(LINGO1):c.-13+4520T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,812 control chromosomes in the GnomAD database, including 14,482 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 0.42 (14482 hom., cov: 31)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_001301186.2	c.-13+4520T>C		intron_variant
LINGO1	NM_001301187.2	c.-13+4520T>C		intron_variant
LINGO1	NM_001301189.2	c.-13+4520T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000561030.5	c.-13+4520T>C		intron_variant		1		P4
LINGO1	ENST00000559893.5	c.-13+4520T>C		intron_variant		4
LINGO1	ENST00000561686.5	c.-13+18151T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63666 AN: 151694 Hom.: 14461 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.420 AC: 63737 AN: 151812 Hom.: 14482 Cov.: 31 AF XY: 0.421 AC XY: 31223 AN XY: 74168

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.421

Alfa AF: 0.385 Hom.: 3391

Bravo AF: 0.429

Asia WGS AF: 0.409 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.1
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7176315; hg19: chr15-77964911;