chr11-40422020-C-T

Position:

• chr11-40422020-C-T

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-269-102299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,130 control chromosomes in the GnomAD database, including 11,564 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 0.38 (11564 hom., cov: 33)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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 (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC4C	NM_001258419.2	c.-269-102299G>A		intron_variant		ENST00000528697.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-269-102299G>A		intron_variant		1	NM_001258419.2	P1
LRRC4C	ENST00000530763.5	c.-189-102299G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58454 AN: 152012 Hom.: 11563 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.384 AC: 58474 AN: 152130 Hom.: 11564 Cov.: 33 AF XY: 0.387 AC XY: 28811 AN XY: 74374

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.392

Alfa AF: 0.394 Hom.: 2486

Bravo AF: 0.379

Asia WGS AF: 0.424 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.69

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: rs1371671; hg19: chr11-40443570;