rs2271396

chr15-77615193-C-Gchr15-77615193-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032808.7(LINGO1):c.714G>C(p.Leu238=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,613,362 control chromosomes in the GnomAD database, including 336,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (32816 hom., cov: 31)
  • Exomes 𝑓: 0.64 (304007 hom.)
• Consequence: LINGO1 NM_032808.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 15-77615193-C-G is Benign according to our data. Variant chr15-77615193-C-G is described in ClinVar as [Benign]. Clinvar id is 1272696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.096 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_032808.7	c.714G>C	p.Leu238=	synonymous_variant	2/2	ENST00000355300.7
LOC105370906	XR_001751806.2	n.689-15092C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000355300.7	c.714G>C	p.Leu238=	synonymous_variant	2/2	1	NM_032808.7	A1
LINGO1	ENST00000561030.5	c.696G>C	p.Leu232=	synonymous_variant	4/4	1		P4
LINGO1	ENST00000557798.1	c.729G>C	p.Leu243=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99671 AN: 151824 Hom.: 32788 Cov.: 31

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.652

GnomAD3 exomes AF: 0.667 AC: 166269 AN: 249182 Hom.: 55989 AF XY: 0.674 AC XY: 91098 AN XY: 135178

Gnomad AFR exome AF: 0.673

Gnomad AMR exome AF: 0.623

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.787

Gnomad SAS exome AF: 0.774

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.643 AC: 939261 AN: 1461420 Hom.: 304007 Cov.: 56 AF XY: 0.648 AC XY: 470920 AN XY: 727010

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.795

Gnomad4 SAS exome AF: 0.778

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.647

GnomAD4 genome AF: 0.657 AC: 99750 AN: 151942 Hom.: 32816 Cov.: 31 AF XY: 0.662 AC XY: 49144 AN XY: 74240

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.651

Alfa AF: 0.609 Hom.: 7568

Bravo AF: 0.652

Asia WGS AF: 0.734 AC: 2551 AN: 3478

EpiCase AF: 0.639

EpiControl AF: 0.637

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2019

- -

Intellectual disability, autosomal recessive 64 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	4.8
Dann	Benign	0.69

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: rs2271396; hg19: chr15-77907535; COSMIC: COSV62437985; COSMIC: COSV62437985;