rs959632

Variant names:

• chr11-41333435-G-A
• rs959632
• NM_001258419.2:c.-496+125996C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.91).
• 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 rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-496+125996C>T		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.-496+125996C>T		intron_variant	Intron 1 of 6	1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-327+125996C>T		intron_variant	Intron 1 of 4	1		ENSP00000434761.1
LRRC4C	ENST00000534577.1	n.207-110427C>T		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.177 AC: 7358 AN: 41500

American (AMR) AF: 0.278 AC: 4253 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2316 AN: 5166

South Asian (SAS) AF: 0.187 AC: 901 AN: 4816

European-Finnish (FIN) AF: 0.224 AC: 2364 AN: 10576

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11952 AN: 67976

Other (OTH) AF: 0.181 AC: 382 AN: 2112

Alfa AF: 0.197 Hom.: 532

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
PhyloP100		0.81
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: rs959632; hg19: chr11-41354985;