11-40247416-C-T

Position:

• chr11-40247416-C-T

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-175-5818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,106 control chromosomes in the GnomAD database, including 46,279 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 0.75 (46279 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-175-5818G>A		intron_variant		ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-175-5818G>A		intron_variant		1	NM_001258419.2	ENSP00000437132	P1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113464 AN: 151988 Hom.: 46280 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.746 AC: 113490 AN: 152106 Hom.: 46279 Cov.: 32 AF XY: 0.750 AC XY: 55718 AN XY: 74338

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.793

Alfa AF: 0.806 Hom.: 6130

Bravo AF: 0.730

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.48

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: rs2861891; hg19: chr11-40268966;