rs11856978

Variant names:

• chr15-77620829-C-G
• rs11856978
• NM_032808.7:c.7-4929G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-77620829-C-G
• chr15-77620829-C-T

Variant summary

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

The NM_032808.7(LINGO1):​c.7-4929G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,888 control chromosomes in the GnomAD database, including 7,218 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 0.24 (7218 hom., cov: 32)
• Consequence: LINGO1 NM_032808.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC105370906 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO1	NM_032808.7	c.7-4929G>C		intron_variant	Intron 1 of 1	ENST00000355300.7	NP_116197.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000355300.7	c.7-4929G>C		intron_variant	Intron 1 of 1	1	NM_032808.7	ENSP00000347451.6

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36379 AN: 151770 Hom.: 7190 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.240 AC: 36462 AN: 151888 Hom.: 7218 Cov.: 32 AF XY: 0.240 AC XY: 17808 AN XY: 74220

African (AFR) AF: 0.548 AC: 22695 AN: 41390

American (AMR) AF: 0.186 AC: 2832 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3466

East Asian (EAS) AF: 0.143 AC: 735 AN: 5136

South Asian (SAS) AF: 0.131 AC: 630 AN: 4818

European-Finnish (FIN) AF: 0.149 AC: 1570 AN: 10550

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7065 AN: 67952

Other (OTH) AF: 0.201 AC: 424 AN: 2106

Alfa AF: 0.0582 Hom.: 64

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.25
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11856978; hg19: chr15-77913171;