11-40477020-C-A

Variant names:

• chr11-40477020-C-A
• rs2119179
• NM_001258419.2:c.-269-157299G>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.-269-157299G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,052 control chromosomes in the GnomAD database, including 1,272 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 0.12 (1272 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• 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]

ENSG00000293027 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-269-157299G>T		intron_variant	Intron 3 of 6	ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-269-157299G>T		intron_variant	Intron 3 of 6	1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-189-157299G>T		intron_variant	Intron 2 of 4	1		ENSP00000434761.1
ENSG00000293027	ENST00000650272.1	n.161-28992G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18942 AN: 151934 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.125 AC: 18976 AN: 152052 Hom.: 1272 Cov.: 32 AF XY: 0.123 AC XY: 9151 AN XY: 74332

African (AFR) AF: 0.119 AC: 4930 AN: 41482

American (AMR) AF: 0.136 AC: 2071 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3468

East Asian (EAS) AF: 0.149 AC: 768 AN: 5156

South Asian (SAS) AF: 0.0818 AC: 395 AN: 4826

European-Finnish (FIN) AF: 0.0998 AC: 1054 AN: 10564

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8741 AN: 67972

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.126 Hom.: 5351

Bravo AF: 0.127

Asia WGS AF: 0.121 AC: 419 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		-0.13
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: rs2119179; hg19: chr11-40498570;