rs7176315

Variant names:

• chr15-77672569-A-G
• rs7176315
• ENST00000561030.5:c.-13+4520T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.89).
• 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 rank	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-13+4520T>C		intron_variant	Intron 5 of 5		NP_001288115.1
LINGO1	NM_001301187.2	c.-13+4520T>C		intron_variant	Intron 5 of 5		NP_001288116.1
LINGO1	NM_001301189.2	c.-13+4520T>C		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+4520T>C		intron_variant	Intron 3 of 3	1		ENSP00000453853.1
LINGO1	ENST00000561686.5	c.-13+18151T>C		intron_variant	Intron 3 of 3	3		ENSP00000455605.1
LINGO1	ENST00000567726.5	c.-13+4520T>C		intron_variant	Intron 2 of 2	4		ENSP00000454465.1

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

African (AFR) AF: 0.605 AC: 25048 AN: 41418

American (AMR) AF: 0.357 AC: 5450 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3466

East Asian (EAS) AF: 0.379 AC: 1946 AN: 5136

South Asian (SAS) AF: 0.352 AC: 1689 AN: 4802

European-Finnish (FIN) AF: 0.336 AC: 3546 AN: 10542

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23176 AN: 67878

Other (OTH) AF: 0.421 AC: 885 AN: 2104

Alfa AF: 0.392 Hom.: 3875

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
PhyloP100		-0.53
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: rs7176315; hg19: chr15-77964911;