rs2271396

Variant names:

• chr15-77615193-C-G
• rs2271396
• NM_032808.7:c.714G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-77615193-C-G
• chr15-77615193-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032808.7(LINGO1):​c.714G>C​(p.Leu238Leu) 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:3
• Conservation: PhyloP100: 0.0960
• Publications: 22 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: Benign. The variant received -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 VariationId 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.

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.714G>C	p.Leu238Leu	synonymous	Exon 2 of 2	NP_116197.4
	LINGO1	NM_001301186.2		c.696G>C	p.Leu232Leu	synonymous	Exon 6 of 6	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.696G>C	p.Leu232Leu	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.714G>C	p.Leu238Leu	synonymous	Exon 2 of 2	ENSP00000347451.6	Q96FE5-1
	LINGO1	ENST00000561030.5	TSL:1	c.696G>C	p.Leu232Leu	synonymous	Exon 4 of 4	ENSP00000453853.1	Q96FE5-2
	LINGO1	ENST00000557798.1	TSL:3	c.729G>C	p.Leu243Leu	synonymous	Exon 2 of 2	ENSP00000453780.1	H0YMX3

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

GnomAD2 exomes AF: 0.667 AC: 166269 AN: 249182 AF XY: 0.674

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 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

African (AFR) AF: 0.685 AC: 22919 AN: 33480

American (AMR) AF: 0.627 AC: 28044 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 16290 AN: 26136

East Asian (EAS) AF: 0.795 AC: 31577 AN: 39700

South Asian (SAS) AF: 0.778 AC: 67132 AN: 86254

European-Finnish (FIN) AF: 0.665 AC: 35457 AN: 53304

Middle Eastern (MID) AF: 0.673 AC: 3880 AN: 5768

European-Non Finnish (NFE) AF: 0.625 AC: 694908 AN: 1111700

Other (OTH) AF: 0.647 AC: 39054 AN: 60358

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

African (AFR) AF: 0.672 AC: 27851 AN: 41452

American (AMR) AF: 0.654 AC: 9982 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2175 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4013 AN: 5136

South Asian (SAS) AF: 0.789 AC: 3795 AN: 4808

European-Finnish (FIN) AF: 0.670 AC: 7075 AN: 10558

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42721 AN: 67944

Other (OTH) AF: 0.651 AC: 1373 AN: 2108

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Intellectual disability, autosomal recessive 64 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.8
DANN	Benign	0.69
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

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