11-41042499-A-G

Variant names:

• chr11-41042499-A-G
• rs1381578
• NM_001258419.2:c.-495-108776T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001258419.2(LRRC4C):​c.-495-108776T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,998 control chromosomes in the GnomAD database, including 11,989 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 0.38 (11989 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	NM_001258419.2	MANE Select	c.-495-108776T>C		intron	N/A	NP_001245348.1	Q9HCJ2
	LRRC4C	NM_020929.3		c.-326-394221T>C		intron	N/A	NP_065980.1	Q9HCJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.-495-108776T>C		intron	N/A	ENSP00000437132.1	Q9HCJ2
	LRRC4C	ENST00000530763.5	TSL:1	c.-326-394221T>C		intron	N/A	ENSP00000434761.1	Q9HCJ2
	LRRC4C	ENST00000534577.1	TSL:3	n.419-108776T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57901 AN: 151880 Hom.: 11999 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.381 AC: 57908 AN: 151998 Hom.: 11989 Cov.: 32 AF XY: 0.389 AC XY: 28875 AN XY: 74282

African (AFR) AF: 0.219 AC: 9095 AN: 41502

American (AMR) AF: 0.406 AC: 6194 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2659 AN: 5164

South Asian (SAS) AF: 0.502 AC: 2420 AN: 4818

European-Finnish (FIN) AF: 0.552 AC: 5831 AN: 10560

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29101 AN: 67916

Other (OTH) AF: 0.380 AC: 800 AN: 2106

Alfa AF: 0.418 Hom.: 7200

Bravo AF: 0.361

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.72
PhyloP100		3.1
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: rs1381578; hg19: chr11-41064049;