chr15-77689122-A-G

Variant names:

• chr15-77689122-A-G
• rs4886894
• ENST00000561030.5:c.-99+1598T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561030.5(LINGO1):​c.-99+1598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,120 control chromosomes in the GnomAD database, including 5,252 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 0.26 (5252 hom., cov: 32)
• Consequence: LINGO1 ENST00000561030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561030.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	NM_001301186.2		c.-99+1598T>C		intron	N/A	NP_001288115.1
	LINGO1	NM_001301187.2		c.-99+1598T>C		intron	N/A	NP_001288116.1
	LINGO1	NM_001301189.2		c.-99+1598T>C		intron	N/A	NP_001288118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000561030.5	TSL:1	c.-99+1598T>C		intron	N/A	ENSP00000453853.1
	LINGO1	ENST00000561686.5	TSL:3	c.-13+1598T>C		intron	N/A	ENSP00000455605.1
	LINGO1	ENST00000567726.5	TSL:4	c.-98-11948T>C		intron	N/A	ENSP00000454465.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39075 AN: 152002 Hom.: 5254 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.257 AC: 39098 AN: 152120 Hom.: 5252 Cov.: 32 AF XY: 0.257 AC XY: 19145 AN XY: 74350

African (AFR) AF: 0.173 AC: 7182 AN: 41526

American (AMR) AF: 0.294 AC: 4491 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1136 AN: 5162

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4814

European-Finnish (FIN) AF: 0.258 AC: 2727 AN: 10572

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20198 AN: 67986

Other (OTH) AF: 0.291 AC: 613 AN: 2108

Alfa AF: 0.291 Hom.: 11140

Bravo AF: 0.257

Asia WGS AF: 0.267 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.34
PhyloP100		-0.15
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: rs4886894; hg19: chr15-77981464;