rs907400

Positions:

• chr15-77620066-C-A
• chr15-77620066-C-T

Variant summary

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

The ENST00000355300.7(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 ENST00000355300.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO1	NM_032808.7	c.7-4166G>T		intron_variant		ENST00000355300.7	NP_116197.4
LOC105370906	XR_001751806.2	n.689-10219C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000355300.7	c.7-4166G>T		intron_variant		1	NM_032808.7	ENSP00000347451	A1

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

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.880

Alfa AF: 0.854 Hom.: 31178

Bravo AF: 0.887

Asia WGS AF: 0.965 AC: 3356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.80

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: rs907400; hg19: chr15-77912408;