15-77613862-T-C

Position:

• chr15-77613862-T-C

Variant summary

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

The NM_032808.7(LINGO1):​c.*182A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 613,578 control chromosomes in the GnomAD database, including 31,389 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 0.30 (6722 hom., cov: 30)
  • Exomes 𝑓: 0.32 (24667 hom.)
• Consequence: LINGO1 NM_032808.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO1	NM_032808.7	c.*182A>G		3_prime_UTR_variant	2/2	ENST00000355300.7	NP_116197.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO1	ENST00000355300.7	c.*182A>G		3_prime_UTR_variant	2/2	1	NM_032808.7	ENSP00000347451.6
LINGO1	ENST00000561030.5	c.*182A>G		3_prime_UTR_variant	4/4	1		ENSP00000453853.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 43867 AN: 146624 Hom.: 6722 Cov.: 30

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.320 AC: 149449 AN: 466850 Hom.: 24667 Cov.: 5 AF XY: 0.316 AC XY: 77148 AN XY: 244412

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.299 AC: 43882 AN: 146728 Hom.: 6722 Cov.: 30 AF XY: 0.297 AC XY: 21262 AN XY: 71484

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.294

Alfa AF: 0.315 Hom.: 7543

Bravo AF: 0.288

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3144; hg19: chr15-77906204; COSMIC: COSV62438736; COSMIC: COSV62438736;