rs11856978

Positions:

• chr15-77620829-C-G
• chr15-77620829-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032808.7(LINGO1):​c.7-4929G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,888 control chromosomes in the GnomAD database, including 7,218 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 0.24 (7218 hom., cov: 32)
• Consequence: LINGO1 NM_032808.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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]

LOC105370906 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_032808.7	c.7-4929G>C		intron_variant		ENST00000355300.7
LOC105370906	XR_001751806.2	n.689-9456C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000355300.7	c.7-4929G>C		intron_variant		1	NM_032808.7	A1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36379 AN: 151770 Hom.: 7190 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.240 AC: 36462 AN: 151888 Hom.: 7218 Cov.: 32 AF XY: 0.240 AC XY: 17808 AN XY: 74220

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.201

Alfa AF: 0.0582 Hom.: 64

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs11856978; hg19: chr15-77913171;