rs9652490

Positions:

• chr15-77671545-A-G
• chr15-77671545-A-T

Variant summary

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

The ENST00000561030.5(LINGO1):​c.-13+5544T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,208 control chromosomes in the GnomAD database, including 6,914 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 0.28 (6914 hom., cov: 34)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-13+5544T>C		intron_variant			NP_001288115.1
LINGO1	NM_001301187.2	c.-13+5544T>C		intron_variant			NP_001288116.1
LINGO1	NM_001301189.2	c.-13+5544T>C		intron_variant			NP_001288118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000561030.5	c.-13+5544T>C		intron_variant		1		ENSP00000453853	P4
LINGO1	ENST00000559893.5	c.-13+5544T>C		intron_variant		4		ENSP00000454051
LINGO1	ENST00000561686.5	c.-13+19175T>C		intron_variant		3		ENSP00000455605

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42225 AN: 152090 Hom.: 6895 Cov.: 34

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.278 AC: 42287 AN: 152208 Hom.: 6914 Cov.: 34 AF XY: 0.277 AC XY: 20621 AN XY: 74422

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.261

Alfa AF: 0.221 Hom.: 9020

Bravo AF: 0.279

Asia WGS AF: 0.257 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.0
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9652490; hg19: chr15-77963887;