rs2271398

Variant names:

• chr15-77615442-G-A
• rs2271398
• NM_032808.7:c.465C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-77615442-G-A
• chr15-77615442-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032808.7(LINGO1):​c.465C>T​(p.Ile155Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,613,138 control chromosomes in the GnomAD database, including 335,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32515 hom., cov: 33)
  • Exomes 𝑓: 0.64 (302909 hom.)
• Consequence: LINGO1 NM_032808.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.436
• Publications: 22 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 15-77615442-G-A is Benign according to our data. Variant chr15-77615442-G-A is described in ClinVar as Benign. ClinVar VariationId is 1248197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.436 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.768 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.465C>T	p.Ile155Ile	synonymous	Exon 2 of 2	NP_116197.4
	LINGO1	NM_001301186.2		c.447C>T	p.Ile149Ile	synonymous	Exon 6 of 6	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.447C>T	p.Ile149Ile	synonymous	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.465C>T	p.Ile155Ile	synonymous	Exon 2 of 2	ENSP00000347451.6	Q96FE5-1
	LINGO1	ENST00000561030.5	TSL:1	c.447C>T	p.Ile149Ile	synonymous	Exon 4 of 4	ENSP00000453853.1	Q96FE5-2
	LINGO1	ENST00000557798.1	TSL:3	c.480C>T	p.Ile160Ile	synonymous	Exon 2 of 2	ENSP00000453780.1	H0YMX3

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99155 AN: 151566 Hom.: 32486 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.652

GnomAD2 exomes AF: 0.666 AC: 165846 AN: 249108 AF XY: 0.672

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.783

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.660

GnomAD4 exome AF: 0.642 AC: 937627 AN: 1461452 Hom.: 302909 Cov.: 61 AF XY: 0.647 AC XY: 470088 AN XY: 727018

African (AFR) AF: 0.683 AC: 22875 AN: 33478

American (AMR) AF: 0.626 AC: 28003 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 16204 AN: 26134

East Asian (EAS) AF: 0.782 AC: 31053 AN: 39696

South Asian (SAS) AF: 0.778 AC: 67091 AN: 86258

European-Finnish (FIN) AF: 0.665 AC: 35479 AN: 53374

Middle Eastern (MID) AF: 0.671 AC: 3865 AN: 5764

European-Non Finnish (NFE) AF: 0.624 AC: 694062 AN: 1111668

Other (OTH) AF: 0.646 AC: 38995 AN: 60362

GnomAD4 genome AF: 0.654 AC: 99236 AN: 151686 Hom.: 32515 Cov.: 33 AF XY: 0.660 AC XY: 48919 AN XY: 74154

African (AFR) AF: 0.670 AC: 27691 AN: 41338

American (AMR) AF: 0.652 AC: 9945 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2151 AN: 3464

East Asian (EAS) AF: 0.773 AC: 3960 AN: 5126

South Asian (SAS) AF: 0.789 AC: 3797 AN: 4812

European-Finnish (FIN) AF: 0.667 AC: 7039 AN: 10554

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42514 AN: 67818

Other (OTH) AF: 0.651 AC: 1374 AN: 2110

Alfa AF: 0.638 Hom.: 16654

Bravo AF: 0.651

Asia WGS AF: 0.729 AC: 2533 AN: 3476

EpiCase AF: 0.638

EpiControl AF: 0.636

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Intellectual disability, autosomal recessive 64 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.3
DANN	Benign	0.83
PhyloP100		0.44
Mutation Taster		=84/16	polymorphism (auto)

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: rs2271398; hg19: chr15-77907784; COSMIC: COSV105272513; COSMIC: COSV105272513;