rs11853548

Variant names:

• chr15-77614332-G-A
• rs11853548
• NM_032808.7:c.1575C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-77614332-G-A
• chr15-77614332-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000355300.7(LINGO1):​c.1575C>T​(p.Pro525Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,613,946 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (40 hom.)
• Consequence: LINGO1 ENST00000355300.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.89
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-77614332-G-A is Benign according to our data. Variant chr15-77614332-G-A is described in ClinVar as Benign. ClinVar VariationId is 778558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.89 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1812/152346) while in subpopulation AFR AF = 0.0409 (1701/41582). AF 95% confidence interval is 0.0393. There are 33 homozygotes in GnomAd4. There are 843 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355300.7. 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.1575C>T	p.Pro525Pro	synonymous	Exon 2 of 2	NP_116197.4
	LINGO1	NM_001301186.2		c.1557C>T	p.Pro519Pro	synonymous	Exon 6 of 6	NP_001288115.1
	LINGO1	NM_001301187.2		c.1557C>T	p.Pro519Pro	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.1575C>T	p.Pro525Pro	synonymous	Exon 2 of 2	ENSP00000347451.6
	LINGO1	ENST00000561030.5	TSL:1	c.1557C>T	p.Pro519Pro	synonymous	Exon 4 of 4	ENSP00000453853.1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1805 AN: 152228 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00315 AC: 783 AN: 248782 AF XY: 0.00241

Gnomad AFR exome AF: 0.0446

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000827

GnomAD4 exome AF: 0.00120 AC: 1756 AN: 1461600 Hom.: 40 Cov.: 31 AF XY: 0.00103 AC XY: 752 AN XY: 727078

African (AFR) AF: 0.0428 AC: 1432 AN: 33480

American (AMR) AF: 0.00246 AC: 110 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111864

Other (OTH) AF: 0.00215 AC: 130 AN: 60374

GnomAD4 genome AF: 0.0119 AC: 1812 AN: 152346 Hom.: 33 Cov.: 33 AF XY: 0.0113 AC XY: 843 AN XY: 74498

African (AFR) AF: 0.0409 AC: 1701 AN: 41582

American (AMR) AF: 0.00516 AC: 79 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68018

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00715 Hom.: 18

Bravo AF: 0.0137

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	LINGO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		2.9
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11853548; hg19: chr15-77906674;