chr11-40128057-T-G

Variant names:

• chr11-40128057-T-G
• rs1381566
• NM_001258419.2:c.-42-11723A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258419.2(LRRC4C):​c.-42-11723A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,106 control chromosomes in the GnomAD database, including 2,748 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 0.18 (2748 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	NM_001258419.2	MANE Select	c.-42-11723A>C		intron	N/A	NP_001245348.1
	LRRC4C	NM_020929.3		c.-42-11723A>C		intron	N/A	NP_065980.1
	LRRC4C	NR_047673.1		n.992-11723A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.-42-11723A>C		intron	N/A	ENSP00000437132.1
	LRRC4C	ENST00000278198.2	TSL:1	c.-42-11723A>C		intron	N/A	ENSP00000278198.1
	LRRC4C	ENST00000527150.5	TSL:1	c.-42-11723A>C		intron	N/A	ENSP00000436976.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28066 AN: 151992 Hom.: 2746 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.185 AC: 28091 AN: 152106 Hom.: 2748 Cov.: 32 AF XY: 0.181 AC XY: 13475 AN XY: 74366

African (AFR) AF: 0.203 AC: 8412 AN: 41478

American (AMR) AF: 0.176 AC: 2685 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3468

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5156

South Asian (SAS) AF: 0.0824 AC: 397 AN: 4820

European-Finnish (FIN) AF: 0.104 AC: 1097 AN: 10592

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12849 AN: 67990

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.143 Hom.: 522

Bravo AF: 0.196

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.65
PhyloP100		0.030
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: rs1381566; hg19: chr11-40149607;