rs11853396

chr15-77613889-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032808.7(LINGO1):c.*155G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 680,042 control chromosomes in the GnomAD database, including 48,434 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 0.39 (12346 hom., cov: 28)
  • Exomes 𝑓: 0.36 (36088 hom.)
• Consequence: LINGO1 NM_032808.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_032808.7	c.*155G>C		3_prime_UTR_variant	2/2	ENST00000355300.7
LOC105370906	XR_001751806.2	n.689-16396C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000355300.7	c.*155G>C		3_prime_UTR_variant	2/2	1	NM_032808.7	A1
LINGO1	ENST00000561030.5	c.*155G>C		3_prime_UTR_variant	4/4	1		P4

Frequencies

GnomAD3 genomes AF: 0.392 AC: 58865 AN: 149976 Hom.: 12329 Cov.: 28

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.357 AC: 189111 AN: 529950 Hom.: 36088 Cov.: 6 AF XY: 0.365 AC XY: 100554 AN XY: 275378

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.523

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.393 AC: 58935 AN: 150092 Hom.: 12346 Cov.: 28 AF XY: 0.399 AC XY: 29218 AN XY: 73278

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.393

Alfa AF: 0.360 Hom.: 1132

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	12
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11853396; hg19: chr15-77906231;