rs4879257

Variant names:

• chr9-28670040-T-A
• rs4879257
• NM_001258282.3:c.-314+160A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-28670040-T-A
• chr9-28670040-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152570.4(LINGO2):​c.-365+160A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,716 control chromosomes in the GnomAD database, including 12,134 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 0.38 (12134 hom., cov: 32)
• Consequence: LINGO2 NM_152570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 2 publications found

Genes affected

LINGO2 (HGNC:21207): (leucine rich repeat and Ig domain containing 2) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152570.4. 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
	LINGO2	NM_001258282.3	MANE Select	c.-314+160A>T		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-281+160A>T		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-314+160A>T		intron	N/A	NP_001341504.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-314+160A>T		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-365+160A>T		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-529+160A>T		intron	N/A	ENSP00000513695.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57329 AN: 151598 Hom.: 12085 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.379 AC: 57442 AN: 151716 Hom.: 12134 Cov.: 32 AF XY: 0.383 AC XY: 28411 AN XY: 74120

African (AFR) AF: 0.551 AC: 22804 AN: 41410

American (AMR) AF: 0.473 AC: 7195 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3468

East Asian (EAS) AF: 0.399 AC: 2056 AN: 5152

South Asian (SAS) AF: 0.325 AC: 1561 AN: 4808

European-Finnish (FIN) AF: 0.343 AC: 3616 AN: 10530

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18509 AN: 67828

Other (OTH) AF: 0.355 AC: 743 AN: 2094

Alfa AF: 0.197 Hom.: 433

Bravo AF: 0.397

Asia WGS AF: 0.419 AC: 1445 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
DANN	Benign	0.36
PhyloP100		-0.51
PromoterAI		0.0082	Neutral
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: rs4879257; hg19: chr9-28670038;