rs4488182

Variant names:

• chr11-41054011-T-G
• rs4488182
• NM_001258419.2:c.-495-120288A>C

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-495-120288A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,180 control chromosomes in the GnomAD database, including 2,860 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 0.19 (2860 hom., cov: 33)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 5 publications found

Genes affected

LRRC4C (HGNC:29317): (leucine rich repeat containing 4C) NGL1 is a specific binding partner for netrin G1 (NTNG1; MIM 608818), which is a member of the netrin family of axon guidance molecules (Lin et al., 2003 [PubMed 14595443]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-495-120288A>C		intron_variant	Intron 1 of 6	ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-495-120288A>C		intron_variant	Intron 1 of 6	1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-327+405420A>C		intron_variant	Intron 1 of 4	1		ENSP00000434761.1
LRRC4C	ENST00000534577.1	n.419-120288A>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28230 AN: 152060 Hom.: 2854 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.186 AC: 28244 AN: 152180 Hom.: 2860 Cov.: 33 AF XY: 0.185 AC XY: 13780 AN XY: 74402

African (AFR) AF: 0.131 AC: 5440 AN: 41542

American (AMR) AF: 0.155 AC: 2366 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1084 AN: 5164

South Asian (SAS) AF: 0.139 AC: 671 AN: 4818

European-Finnish (FIN) AF: 0.205 AC: 2171 AN: 10596

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14664 AN: 67994

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.210 Hom.: 5509

Bravo AF: 0.181

Asia WGS AF: 0.144 AC: 497 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.72
PhyloP100		-0.47
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: rs4488182; hg19: chr11-41075561;