rs10837504

Variant names:

• chr11-40797556-C-A
• rs10837504
• NM_001258419.2:c.-407+136079G>T

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-407+136079G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,940 control chromosomes in the GnomAD database, including 10,207 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 0.30 (10207 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-407+136079G>T		intron_variant	Intron 2 of 6	ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-407+136079G>T		intron_variant	Intron 2 of 6	1	NM_001258419.2	ENSP00000437132.1
LRRC4C	ENST00000530763.5	c.-326-149278G>T		intron_variant	Intron 1 of 4	1		ENSP00000434761.1
LRRC4C	ENST00000534577.1	n.507+136079G>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45829 AN: 151820 Hom.: 10162 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.302 AC: 45950 AN: 151940 Hom.: 10207 Cov.: 32 AF XY: 0.301 AC XY: 22329 AN XY: 74258

African (AFR) AF: 0.632 AC: 26194 AN: 41434

American (AMR) AF: 0.209 AC: 3179 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.189 AC: 975 AN: 5170

South Asian (SAS) AF: 0.205 AC: 987 AN: 4818

European-Finnish (FIN) AF: 0.171 AC: 1801 AN: 10550

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11214 AN: 67936

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.217 Hom.: 13131

Bravo AF: 0.319

Asia WGS AF: 0.231 AC: 803 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.49
PhyloP100		-0.70
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: rs10837504; hg19: chr11-40819106;