chr11-40115200-C-T

Variant names:

• chr11-40115200-C-T
• rs761164531
• NM_001258419.2:c.1093G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001258419.2(LRRC4C):​c.1093G>A​(p.Val365Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC4C NM_001258419.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87
• Publications: 0 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]

ENSG00000306946 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19011584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258419.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	NM_001258419.2	MANE Select	c.1093G>A	p.Val365Ile	missense	Exon 7 of 7	NP_001245348.1	Q9HCJ2
	LRRC4C	NM_020929.3		c.1093G>A	p.Val365Ile	missense	Exon 5 of 5	NP_065980.1	Q9HCJ2
	LRRC4C	NR_047673.1		n.2126G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.1093G>A	p.Val365Ile	missense	Exon 7 of 7	ENSP00000437132.1	Q9HCJ2
	LRRC4C	ENST00000278198.2	TSL:1	c.1093G>A	p.Val365Ile	missense	Exon 2 of 2	ENSP00000278198.1	Q9HCJ2
	LRRC4C	ENST00000527150.5	TSL:1	c.1093G>A	p.Val365Ile	missense	Exon 3 of 3	ENSP00000436976.1	Q9HCJ2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250762 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.066	T
Eigen	Benign	0.057
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.13
Sift	Benign	0.46	T
Sift4G	Benign	0.54	T
Polyphen		0.013	B
Vest4		0.23
MutPred		0.73		Loss of catalytic residue at V365 (P = 0.127)
MVP		0.32
MPC		0.59
ClinPred		0.25	T
GERP RS		5.7
Varity_R		0.27
gMVP		0.62
Mutation Taster		=73/27	polymorphism

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: rs761164531; hg19: chr11-40136750;