rs11602008

Variant names:

• chr11-40127755-A-T
• rs11602008
• NM_001258419.2:c.-42-11421T>A

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-42-11421T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,084 control chromosomes in the GnomAD database, including 2,238 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 0.17 (2238 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 12 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-42-11421T>A		intron_variant	Intron 6 of 6	ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-42-11421T>A		intron_variant	Intron 6 of 6	1	NM_001258419.2	ENSP00000437132.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25325 AN: 151966 Hom.: 2236 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.167 AC: 25346 AN: 152084 Hom.: 2238 Cov.: 32 AF XY: 0.163 AC XY: 12123 AN XY: 74346

African (AFR) AF: 0.187 AC: 7758 AN: 41480

American (AMR) AF: 0.158 AC: 2411 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3466

East Asian (EAS) AF: 0.263 AC: 1357 AN: 5150

South Asian (SAS) AF: 0.0663 AC: 320 AN: 4824

European-Finnish (FIN) AF: 0.0965 AC: 1023 AN: 10600

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11372 AN: 67968

Other (OTH) AF: 0.160 AC: 336 AN: 2104

Alfa AF: 0.164 Hom.: 264

Bravo AF: 0.178

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.44
DANN	Benign	0.85
PhyloP100		-0.75
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: rs11602008; hg19: chr11-40149305;