NM_032808.7:c.885C>T

Variant names:

• chr15-77615022-G-A
• rs34904447
• NM_032808.7:c.885C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032808.7(LINGO1):​c.885C>T​(p.Ser295Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: LINGO1 NM_032808.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

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.885C>T	p.Ser295Ser	synonymous	Exon 2 of 2	NP_116197.4
	LINGO1	NM_001301186.2		c.867C>T	p.Ser289Ser	synonymous	Exon 6 of 6	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.867C>T	p.Ser289Ser	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.885C>T	p.Ser295Ser	synonymous	Exon 2 of 2	ENSP00000347451.6	Q96FE5-1
	LINGO1	ENST00000561030.5	TSL:1	c.867C>T	p.Ser289Ser	synonymous	Exon 4 of 4	ENSP00000453853.1	Q96FE5-2
	LINGO1	ENST00000557798.1	TSL:3	c.900C>T	p.Ser300Ser	synonymous	Exon 2 of 2	ENSP00000453780.1	H0YMX3

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000762 AC: 19 AN: 249278 AF XY: 0.0000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000187 AC: 273 AN: 1461704 Hom.: 0 Cov.: 56 AF XY: 0.000188 AC XY: 137 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000241 AC: 268 AN: 1111866

Other (OTH) AF: 0.0000828 AC: 5 AN: 60374

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000148 Hom.: 0

Bravo AF: 0.0000831

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		1.9

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: rs34904447; hg19: chr15-77907364; COSMIC: COSV62439002; COSMIC: COSV62439002;