11-40128057-T-G

Position:

• chr11-40128057-T-G

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-42-11723A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,106 control chromosomes in the GnomAD database, including 2,748 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 0.18 (2748 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-42-11723A>C		intron_variant		ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-42-11723A>C		intron_variant		1	NM_001258419.2	ENSP00000437132	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28066 AN: 151992 Hom.: 2746 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.185 AC: 28091 AN: 152106 Hom.: 2748 Cov.: 32 AF XY: 0.181 AC XY: 13475 AN XY: 74366

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.180

Alfa AF: 0.0795 Hom.: 111

Bravo AF: 0.196

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.65

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: rs1381566; hg19: chr11-40149607;