chr1-151800911-G-A

Position:

• chr1-151800911-G-A

Variant summary

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

The NM_001004432.4(LINGO4):​c.*12C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,585,980 control chromosomes in the GnomAD database, including 7,100 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 0.058 (819 hom., cov: 33)
  • Exomes 𝑓: 0.034 (6281 hom.)
• Consequence: LINGO4 NM_001004432.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

Genes affected

LINGO4 (HGNC:31814): (leucine rich repeat and Ig domain containing 4) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO4	NM_001004432.4	c.*12C>T		3_prime_UTR_variant	2/2	ENST00000368820.4	NP_001004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO4	ENST00000368820.4	c.*12C>T		3_prime_UTR_variant	2/2	1	NM_001004432.4	ENSP00000357810	P1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8824 AN: 152098 Hom.: 821 Cov.: 33

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.0573

GnomAD3 exomes AF: 0.100 AC: 23141 AN: 231370 Hom.: 3394 AF XY: 0.0959 AC XY: 11980 AN XY: 124950

Gnomad AFR exome AF: 0.0906

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.391

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.000490

Gnomad NFE exome AF: 0.00274

Gnomad OTH exome AF: 0.0586

GnomAD4 exome AF: 0.0343 AC: 49229 AN: 1433764 Hom.: 6281 Cov.: 31 AF XY: 0.0383 AC XY: 27218 AN XY: 709742

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.00193

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.000383

Gnomad4 NFE exome AF: 0.00194

Gnomad4 OTH exome AF: 0.0458

GnomAD4 genome AF: 0.0580 AC: 8821 AN: 152216 Hom.: 819 Cov.: 33 AF XY: 0.0638 AC XY: 4751 AN XY: 74432

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.0562

Alfa AF: 0.0216 Hom.: 62

Bravo AF: 0.0706

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.80

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: rs1521179; hg19: chr1-151773387; COSMIC: COSV64313620; COSMIC: COSV64313620;