11-41124949-A-G

Variant names:

• chr11-41124949-A-G
• rs10837576
• NM_001258419.2:c.-495-191226T>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.-495-191226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,056 control chromosomes in the GnomAD database, including 35,459 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 0.67 (35459 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-495-191226T>C		intron_variant	Intron 1 of 6	ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-495-191226T>C		intron_variant	Intron 1 of 6	1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-327+334482T>C		intron_variant	Intron 1 of 4	1		ENSP00000434761.1
LRRC4C	ENST00000534577.1	n.418+97848T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101798 AN: 151938 Hom.: 35427 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.670 AC: 101868 AN: 152056 Hom.: 35459 Cov.: 32 AF XY: 0.680 AC XY: 50509 AN XY: 74328

African (AFR) AF: 0.485 AC: 20083 AN: 41448

American (AMR) AF: 0.778 AC: 11894 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3470

East Asian (EAS) AF: 0.915 AC: 4716 AN: 5156

South Asian (SAS) AF: 0.814 AC: 3917 AN: 4814

European-Finnish (FIN) AF: 0.814 AC: 8623 AN: 10590

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48151 AN: 67970

Other (OTH) AF: 0.677 AC: 1429 AN: 2112

Alfa AF: 0.689 Hom.: 69066

Bravo AF: 0.659

Asia WGS AF: 0.843 AC: 2930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.52
PhyloP100		-1.8
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: rs10837576; hg19: chr11-41146499;