chr15-77614797-C-T

Variant names:

• chr15-77614797-C-T
• rs61737308
• NM_032808.7:c.1110G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_032808.7(LINGO1):​c.1110G>A​(p.Pro370Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,610,034 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (6 hom., cov: 33)
  • Exomes 𝑓: 0.013 (162 hom.)
• Consequence: LINGO1 NM_032808.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.75
• Publications: 4 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC105370906 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-77614797-C-T is Benign according to our data. Variant chr15-77614797-C-T is described in ClinVar as Benign. ClinVar VariationId is 771195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 Unknown,AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	NM_032808.7	MANE Select	c.1110G>A	p.Pro370Pro	synonymous	Exon 2 of 2	NP_116197.4
	LINGO1	NM_001301186.2		c.1092G>A	p.Pro364Pro	synonymous	Exon 6 of 6	NP_001288115.1
	LINGO1	NM_001301187.2		c.1092G>A	p.Pro364Pro	synonymous	Exon 6 of 6	NP_001288116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000355300.7	TSL:1 MANE Select	c.1110G>A	p.Pro370Pro	synonymous	Exon 2 of 2	ENSP00000347451.6
	LINGO1	ENST00000561030.5	TSL:1	c.1092G>A	p.Pro364Pro	synonymous	Exon 4 of 4	ENSP00000453853.1
	LINGO1	ENST00000557798.1	TSL:3	c.*147G>A		downstream_gene	N/A	ENSP00000453780.1

Frequencies

GnomAD3 genomes AF: 0.00819 AC: 1246 AN: 152226 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00811 AC: 1950 AN: 240436 AF XY: 0.00814

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.00538

Gnomad ASJ exome AF: 0.0172

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00624

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.00933

GnomAD4 exome AF: 0.0130 AC: 18908 AN: 1457690 Hom.: 162 Cov.: 31 AF XY: 0.0126 AC XY: 9125 AN XY: 724738

African (AFR) AF: 0.00216 AC: 72 AN: 33394

American (AMR) AF: 0.00510 AC: 225 AN: 44100

Ashkenazi Jewish (ASJ) AF: 0.0168 AC: 436 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.00295 AC: 252 AN: 85492

European-Finnish (FIN) AF: 0.00597 AC: 317 AN: 53064

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5766

European-Non Finnish (NFE) AF: 0.0152 AC: 16836 AN: 1110144

Other (OTH) AF: 0.0125 AC: 755 AN: 60220

GnomAD4 genome AF: 0.00818 AC: 1246 AN: 152344 Hom.: 6 Cov.: 33 AF XY: 0.00750 AC XY: 559 AN XY: 74502

African (AFR) AF: 0.00236 AC: 98 AN: 41590

American (AMR) AF: 0.00575 AC: 88 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.00602 AC: 64 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 903 AN: 68018

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00902 Hom.: 2

Bravo AF: 0.00844

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LINGO1: BP4, BP7, BS1, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61737308; hg19: chr15-77907139; COSMIC: COSV100796513; COSMIC: COSV100796513;