rs78015633

Positions:

• chr11-40855036-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001258419.2(LRRC4C):​c.-407+78599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0089 in 152,270 control chromosomes in the GnomAD database, including 6 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 0.0089 (6 hom., cov: 33)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0089 (1355/152270) while in subpopulation NFE AF= 0.0159 (1078/67996). AF 95% confidence interval is 0.0151. There are 6 homozygotes in gnomad4. There are 611 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1355 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC4C	NM_001258419.2	c.-407+78599A>G		intron_variant		ENST00000528697.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-407+78599A>G		intron_variant		1	NM_001258419.2	P1
LRRC4C	ENST00000530763.5	c.-326-206758A>G		intron_variant		1		P1
LRRC4C	ENST00000534577.1	n.507+78599A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00891 AC: 1355 AN: 152152 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00829

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00890 AC: 1355 AN: 152270 Hom.: 6 Cov.: 33 AF XY: 0.00821 AC XY: 611 AN XY: 74460

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.00829

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.0115 Hom.: 2

Bravo AF: 0.00836

Asia WGS AF: 0.00202 AC: 7 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.74

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: rs78015633; hg19: chr11-40876586;