15-77617860-G-T

Position:

• chr15-77617860-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032808.7(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 NM_032808.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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]

LOC105370906 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_032808.7	c.7-1960C>A		intron_variant		ENST00000355300.7
LOC105370906	XR_001751806.2	n.689-12425G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000355300.7	c.7-1960C>A		intron_variant		1	NM_032808.7	A1

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

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.634

Alfa AF: 0.623 Hom.: 37454

Bravo AF: 0.631

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs907396; hg19: chr15-77910202;