dbSNP rs11633842: LINGO1-AS1:n.1478G>A (chr15-77648998-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000558691.1(LINGO1-AS1):n.1478G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00866 in 152,340 control chromosomes in the GnomAD database, including 5 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 0.0087 ( 5 hom., cov: 33)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

LINGO1-AS1
ENST00000558691.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.562

Publications

0 publications found

Variant links:

Genes affected

LINGO1-AS1 (HGNC:27368): (LINGO1 antisense RNA 1)

LINGO1-AS1 links:

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

LINGO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
LINGO1-AS1	NR_045123.1 link	n.1478G>A	non_coding_transcript_exon_variant	Exon 3 of 3
LINGO1	NM_001301186.2 link	c.-13+28091C>T	intron_variant	Intron 5 of 5	NP_001288115.1
LINGO1	NM_001301187.2 link	c.-13+28091C>T	intron_variant	Intron 5 of 5	NP_001288116.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
LINGO1-AS1	ENST00000558691.1 link	n.1478G>A	non_coding_transcript_exon_variant	Exon 3 of 3	1
LINGO1	ENST00000561030.5 link	c.-13+28091C>T	intron_variant	Intron 3 of 3	1	ENSP00000453853.1
LINGO1	ENST00000561686.5 link	c.-12-33098C>T	intron_variant	Intron 3 of 3	3	ENSP00000455605.1

Frequencies

GnomAD3 genomes

AF:

0.00867

AC:

1319

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00665

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00860

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00865

AC:

1318

AN:

152328

Hom.:

Cov.:

AF XY:

0.00888

AC XY:

661

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00255

AC:

106

AN:

41584

American (AMR)

AF:

0.00451

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00666

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.0151

AC:

160

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0131

AC:

892

AN:

68028

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

140

211

281

351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00223

Hom.:

Bravo

AF:

0.00748

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.45

(source)

DANN

Benign

0.53

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over