rs4611189

Variant names:

• chr11-40816163-G-A
• rs4611189
• NM_001258419.2:c.-407+117472C>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.-407+117472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 152,232 control chromosomes in the GnomAD database, including 181 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 0.035 (181 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-407+117472C>T		intron_variant	Intron 2 of 6	ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-407+117472C>T		intron_variant	Intron 2 of 6	1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-326-167885C>T		intron_variant	Intron 1 of 4	1		ENSP00000434761.1
LRRC4C	ENST00000534577.1	n.507+117472C>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5247 AN: 152114 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0346 AC: 5267 AN: 152232 Hom.: 181 Cov.: 32 AF XY: 0.0337 AC XY: 2508 AN XY: 74432

African (AFR) AF: 0.0859 AC: 3566 AN: 41518

American (AMR) AF: 0.0242 AC: 370 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5174

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4824

European-Finnish (FIN) AF: 0.00631 AC: 67 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0134 AC: 909 AN: 68020

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0200 Hom.: 241

Bravo AF: 0.0362

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		0.098
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: rs4611189; hg19: chr11-40837713;