15-77613862-T-C

Variant names:

• chr15-77613862-T-C
• rs3144
• NM_032808.7:c.*182A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

LOC105370906 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032808.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	NM_032808.7	MANE Select	c.*182A>G		3_prime_UTR	Exon 2 of 2	NP_116197.4
	LINGO1	NM_001301186.2		c.*182A>G		3_prime_UTR	Exon 6 of 6	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.*182A>G		3_prime_UTR	Exon 6 of 6	NP_001288116.1	Q96FE5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000355300.7	TSL:1 MANE Select	c.*182A>G		3_prime_UTR	Exon 2 of 2	ENSP00000347451.6	Q96FE5-1
	LINGO1	ENST00000561030.5	TSL:1	c.*182A>G		3_prime_UTR	Exon 4 of 4	ENSP00000453853.1	Q96FE5-2

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

African (AFR) AF: 0.195 AC: 2489 AN: 12758

American (AMR) AF: 0.356 AC: 6592 AN: 18530

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 3030 AN: 13764

East Asian (EAS) AF: 0.304 AC: 9447 AN: 31072

South Asian (SAS) AF: 0.240 AC: 10689 AN: 44594

European-Finnish (FIN) AF: 0.335 AC: 9833 AN: 29322

Middle Eastern (MID) AF: 0.219 AC: 443 AN: 2022

European-Non Finnish (NFE) AF: 0.344 AC: 99020 AN: 288200

Other (OTH) AF: 0.297 AC: 7906 AN: 26588

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

African (AFR) AF: 0.216 AC: 8479 AN: 39192

American (AMR) AF: 0.332 AC: 4903 AN: 14774

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 788 AN: 3438

East Asian (EAS) AF: 0.274 AC: 1306 AN: 4764

South Asian (SAS) AF: 0.244 AC: 1085 AN: 4450

European-Finnish (FIN) AF: 0.341 AC: 3352 AN: 9830

Middle Eastern (MID) AF: 0.212 AC: 61 AN: 288

European-Non Finnish (NFE) AF: 0.343 AC: 23004 AN: 67046

Other (OTH) AF: 0.294 AC: 602 AN: 2046

Alfa AF: 0.314 Hom.: 9813

Bravo AF: 0.288

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3144;

hg19: chr15-77906204;

COSMIC: COSV62438736;

COSMIC: COSV62438736;