15-77617860-G-T

Variant names:

• chr15-77617860-G-T
• rs907396
• NM_032808.7:c.7-1960C>A

Variant summary

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

The ENST00000355300.7(LINGO1):​c.7-1960C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,080 control chromosomes in the GnomAD database, including 30,969 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 0.64 (30969 hom., cov: 33)
• Consequence: LINGO1 ENST00000355300.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355300.7. 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_032808.7	MANE Select	c.7-1960C>A		intron	N/A	NP_116197.4
	LINGO1	NM_001301186.2		c.-12-1960C>A		intron	N/A	NP_001288115.1
	LINGO1	NM_001301187.2		c.-12-1960C>A		intron	N/A	NP_001288116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000355300.7	TSL:1 MANE Select	c.7-1960C>A		intron	N/A	ENSP00000347451.6
	LINGO1	ENST00000561030.5	TSL:1	c.-12-1960C>A		intron	N/A	ENSP00000453853.1
	LINGO1	ENST00000557798.1	TSL:3	c.22-1960C>A		intron	N/A	ENSP00000453780.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96795 AN: 151962 Hom.: 30949 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.637 AC: 96867 AN: 152080 Hom.: 30969 Cov.: 33 AF XY: 0.644 AC XY: 47829 AN XY: 74314

African (AFR) AF: 0.645 AC: 26764 AN: 41496

American (AMR) AF: 0.638 AC: 9757 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2047 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4080 AN: 5152

South Asian (SAS) AF: 0.752 AC: 3632 AN: 4830

European-Finnish (FIN) AF: 0.655 AC: 6930 AN: 10578

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41648 AN: 67954

Other (OTH) AF: 0.634 AC: 1340 AN: 2112

Alfa AF: 0.626 Hom.: 49583

Bravo AF: 0.631

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		0.19
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: rs907396; hg19: chr15-77910202; COSMIC: COSV107440014;