rs959632

Positions:

• chr11-41333435-G-A

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-496+125996C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,100 control chromosomes in the GnomAD database, including 3,305 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 0.20 (3305 hom., cov: 33)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809

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]

LRRC4C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-496+125996C>T		intron_variant		ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-496+125996C>T		intron_variant		1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-327+125996C>T		intron_variant		1		ENSP00000434761.1
LRRC4C	ENST00000534577.1	n.207-110427C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30164 AN: 151982 Hom.: 3300 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.199 AC: 30196 AN: 152100 Hom.: 3305 Cov.: 33 AF XY: 0.205 AC XY: 15256 AN XY: 74354

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.181

Alfa AF: 0.198 Hom.: 524

Bravo AF: 0.202

Asia WGS AF: 0.317 AC: 1102 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.67

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: rs959632; hg19: chr11-41354985;