15-77672858-C-G

Variant names:

• chr15-77672858-C-G
• rs7177008
• ENST00000561030.5:c.-13+4231G>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+4231G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,084 control chromosomes in the GnomAD database, including 7,054 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 (7054 hom., cov: 32)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_001301186.2	c.-13+4231G>C		intron_variant	Intron 5 of 5		NP_001288115.1
LINGO1	NM_001301187.2	c.-13+4231G>C		intron_variant	Intron 5 of 5		NP_001288116.1
LINGO1	NM_001301189.2	c.-13+4231G>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+4231G>C		intron_variant	Intron 3 of 3	1		ENSP00000453853.1
LINGO1	ENST00000561686.5	c.-13+17862G>C		intron_variant	Intron 3 of 3	3		ENSP00000455605.1
LINGO1	ENST00000567726.5	c.-13+4231G>C		intron_variant	Intron 2 of 2	4		ENSP00000454465.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42517 AN: 151966 Hom.: 7036 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.280 AC: 42577 AN: 152084 Hom.: 7054 Cov.: 32 AF XY: 0.279 AC XY: 20740 AN XY: 74340

African (AFR) AF: 0.459 AC: 19042 AN: 41458

American (AMR) AF: 0.169 AC: 2590 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1263 AN: 5166

South Asian (SAS) AF: 0.201 AC: 965 AN: 4812

European-Finnish (FIN) AF: 0.220 AC: 2331 AN: 10586

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14857 AN: 67984

Other (OTH) AF: 0.262 AC: 552 AN: 2110

Alfa AF: 0.112 Hom.: 176

Bravo AF: 0.282

Asia WGS AF: 0.258 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.51
PhyloP100		-3.7
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: rs7177008; hg19: chr15-77965200;