dbSNP rs9652490: LINGO1:c.-13+5544T>C (chr15-77671545-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001301186.2(LINGO1):c.-13+5544T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,208 control chromosomes in the GnomAD database, including 6,914 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 0.28 ( 6914 hom., cov: 34)

Consequence

LINGO1
NM_001301186.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.436

Publications

67 publications found

Variant links:

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)

LINGO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301186.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
LINGO1	NM_001301186.2	c.-13+5544T>C	intron	N/A	NP_001288115.1	Q96FE5-2
LINGO1	NM_001301187.2	c.-13+5544T>C	intron	N/A	NP_001288116.1	Q96FE5-2
LINGO1	NM_001301189.2	c.-13+5544T>C	intron	N/A	NP_001288118.1	Q96FE5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LINGO1	ENST00000561030.5	TSL:1	c.-13+5544T>C	intron	N/A	ENSP00000453853.1	Q96FE5-2
LINGO1	ENST00000561686.5	TSL:3	c.-13+19175T>C	intron	N/A	ENSP00000455605.1	H3BQ49
LINGO1	ENST00000567726.5	TSL:4	c.-13+5544T>C	intron	N/A	ENSP00000454465.1	H3BMN3

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42225

AN:

152090

Hom.:

6895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.278

AC:

42287

AN:

152208

Hom.:

6914

Cov.:

AF XY:

0.277

AC XY:

20621

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.452

AC:

18748

AN:

41510

American (AMR)

AF:

0.169

AC:

2582

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

750

AN:

3472

East Asian (EAS)

AF:

0.243

AC:

1258

AN:

5172

South Asian (SAS)

AF:

0.201

AC:

970

AN:

4824

European-Finnish (FIN)

AF:

0.221

AC:

2347

AN:

10618

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14851

AN:

67992

Other (OTH)

AF:

0.261

AC:

551

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1539

3079

4618

6158

7697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.232

Hom.:

20519

Bravo

AF:

0.279

Asia WGS

AF:

0.257

AC:

896

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

7.0

(source)

DANN

Benign

0.26

PhyloP100

0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over