11-41204404-T-G

Variant names:

• chr11-41204404-T-G
• rs980952
• NM_001258419.2:c.-496+255027A>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.-496+255027A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,234 control chromosomes in the GnomAD database, including 67,665 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 0.94 (67665 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-496+255027A>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.-496+255027A>C		intron_variant	Intron 1 of 6	1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-327+255027A>C		intron_variant	Intron 1 of 4	1		ENSP00000434761.1
LRRC4C	ENST00000534577.1	n.418+18393A>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143176 AN: 152116 Hom.: 67617 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.955

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

GnomAD4 genome AF: 0.941 AC: 143281 AN: 152234 Hom.: 67665 Cov.: 32 AF XY: 0.942 AC XY: 70127 AN XY: 74412

African (AFR) AF: 0.856 AC: 35534 AN: 41530

American (AMR) AF: 0.971 AC: 14853 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3386 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5143 AN: 5144

South Asian (SAS) AF: 0.973 AC: 4697 AN: 4826

European-Finnish (FIN) AF: 0.987 AC: 10477 AN: 10616

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.970 AC: 65974 AN: 68032

Other (OTH) AF: 0.955 AC: 2019 AN: 2114

Alfa AF: 0.953 Hom.: 101779

Bravo AF: 0.936

Asia WGS AF: 0.980 AC: 3405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		0.014
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: rs980952; hg19: chr11-41225954;