11-41321635-C-T

Position:

• chr11-41321635-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000528697.6(LRRC4C):​c.-496+137796G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,828 control chromosomes in the GnomAD database, including 13,987 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 0.41 (13987 hom., cov: 31)
• Consequence: LRRC4C ENST00000528697.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-496+137796G>A		intron_variant		ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-496+137796G>A		intron_variant		1	NM_001258419.2	ENSP00000437132	P1
LRRC4C	ENST00000530763.5	c.-327+137796G>A		intron_variant		1		ENSP00000434761	P1
LRRC4C	ENST00000534577.1	n.207-98627G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62673 AN: 151710 Hom.: 13976 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.413 AC: 62708 AN: 151828 Hom.: 13987 Cov.: 31 AF XY: 0.412 AC XY: 30582 AN XY: 74180

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.452

Alfa AF: 0.446 Hom.: 6382

Bravo AF: 0.406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs2044541; hg19: chr11-41343185; COSMIC: COSV73182236;