chr15-77680670-A-C

Variant names:

• chr15-77680670-A-C
• rs11856876
• ENST00000561030.5:c.-98-3496T>G

Variant summary

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

The NM_001301186.2(LINGO1):​c.-98-3496T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,754 control chromosomes in the GnomAD database, including 13,143 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 0.40 (13143 hom., cov: 31)
• Consequence: LINGO1 NM_001301186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 2 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: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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 = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301186.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	NM_001301186.2		c.-98-3496T>G		intron	N/A	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.-98-3496T>G		intron	N/A	NP_001288116.1	Q96FE5-2
	LINGO1	NM_001301189.2		c.-98-3496T>G		intron	N/A	NP_001288118.1	Q96FE5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000561030.5	TSL:1	c.-98-3496T>G		intron	N/A	ENSP00000453853.1	Q96FE5-2
	LINGO1	ENST00000561686.5	TSL:3	c.-13+10050T>G		intron	N/A	ENSP00000455605.1	H3BQ49
	LINGO1	ENST00000567726.5	TSL:4	c.-98-3496T>G		intron	N/A	ENSP00000454465.1	H3BMN3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61282 AN: 151636 Hom.: 13132 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.404 AC: 61337 AN: 151754 Hom.: 13143 Cov.: 31 AF XY: 0.406 AC XY: 30111 AN XY: 74164

African (AFR) AF: 0.554 AC: 22915 AN: 41348

American (AMR) AF: 0.352 AC: 5371 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1587 AN: 3466

East Asian (EAS) AF: 0.374 AC: 1908 AN: 5100

South Asian (SAS) AF: 0.351 AC: 1681 AN: 4786

European-Finnish (FIN) AF: 0.336 AC: 3543 AN: 10560

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23096 AN: 67924

Other (OTH) AF: 0.405 AC: 850 AN: 2098

Alfa AF: 0.315 Hom.: 1903

Bravo AF: 0.412

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.74
PhyloP100		-0.30
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: rs11856876; hg19: chr15-77973012;