ENST00000561030.5:c.-13+5325T>C

Variant names:

• chr15-77671764-A-G
• rs11631120
• ENST00000561030.5:c.-13+5325T>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+5325T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,168 control chromosomes in the GnomAD database, including 1,396 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 0.12 (1396 hom., cov: 34)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	XM_011522118.3	c.-95T>C		5_prime_UTR_variant	Exon 1 of 2		XP_011520420.1
LINGO1	NM_001301186.2	c.-13+5325T>C		intron_variant	Intron 5 of 5		NP_001288115.1
LINGO1	NM_001301187.2	c.-13+5325T>C		intron_variant	Intron 5 of 5		NP_001288116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000561030.5	c.-13+5325T>C		intron_variant	Intron 3 of 3	1		ENSP00000453853.1
LINGO1	ENST00000561686.5	c.-13+18956T>C		intron_variant	Intron 3 of 3	3		ENSP00000455605.1
LINGO1	ENST00000567726.5	c.-13+5325T>C		intron_variant	Intron 2 of 2	4		ENSP00000454465.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18463 AN: 152050 Hom.: 1398 Cov.: 34

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.121 AC: 18460 AN: 152168 Hom.: 1396 Cov.: 34 AF XY: 0.122 AC XY: 9104 AN XY: 74386

African (AFR) AF: 0.0449 AC: 1865 AN: 41544

American (AMR) AF: 0.104 AC: 1585 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3466

East Asian (EAS) AF: 0.109 AC: 561 AN: 5152

South Asian (SAS) AF: 0.102 AC: 491 AN: 4814

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11327 AN: 67966

Other (OTH) AF: 0.127 AC: 269 AN: 2116

Alfa AF: 0.140 Hom.: 231

Bravo AF: 0.111

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.73
PhyloP100		0.17
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: rs11631120; hg19: chr15-77964106;