chr15-77620066-C-A

Variant names:

• chr15-77620066-C-A
• rs907400
• NM_032808.7:c.7-4166G>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.7-4166G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,262 control chromosomes in the GnomAD database, including 59,854 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 0.89 (59854 hom., cov: 34)
• Consequence: LINGO1 NM_032808.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 4 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)

LOC105370906 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032808.7. 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_032808.7	MANE Select	c.7-4166G>T		intron	N/A	NP_116197.4
	LINGO1	NM_001301186.2		c.-12-4166G>T		intron	N/A	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.-12-4166G>T		intron	N/A	NP_001288116.1	Q96FE5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000355300.7	TSL:1 MANE Select	c.7-4166G>T		intron	N/A	ENSP00000347451.6	Q96FE5-1
	LINGO1	ENST00000561030.5	TSL:1	c.-12-4166G>T		intron	N/A	ENSP00000453853.1	Q96FE5-2
	LINGO1	ENST00000557798.1	TSL:3	c.22-4166G>T		intron	N/A	ENSP00000453780.1	H0YMX3

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134627 AN: 152144 Hom.: 59789 Cov.: 34

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.885 AC: 134753 AN: 152262 Hom.: 59854 Cov.: 34 AF XY: 0.891 AC XY: 66353 AN XY: 74448

African (AFR) AF: 0.956 AC: 39737 AN: 41546

American (AMR) AF: 0.888 AC: 13593 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2864 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5182

South Asian (SAS) AF: 0.945 AC: 4564 AN: 4830

European-Finnish (FIN) AF: 0.885 AC: 9390 AN: 10614

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56597 AN: 67994

Other (OTH) AF: 0.880 AC: 1857 AN: 2110

Alfa AF: 0.859 Hom.: 50595

Bravo AF: 0.887

Asia WGS AF: 0.965 AC: 3356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.80
PhyloP100		-1.2
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: rs907400; hg19: chr15-77912408;