11-40114613-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001258419.2(LRRC4C):c.1680C>T(p.His560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,154 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (5 hom.)
• Consequence: LRRC4C NM_001258419.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 11-40114613-G-A is Benign according to our data. Variant chr11-40114613-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.
• BS2: High AC in GnomAd at 170 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC4C	NM_001258419.2	c.1680C>T	p.His560=	synonymous_variant	7/7	ENST00000528697.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC4C	ENST00000528697.6	c.1680C>T	p.His560=	synonymous_variant	7/7	1	NM_001258419.2	P1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 170 AN: 152154 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00117 AC: 293 AN: 250998 Hom.: 0 AF XY: 0.00122 AC XY: 165 AN XY: 135630

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000719

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00190

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00122 AC: 1782 AN: 1461882 Hom.: 5 Cov.: 31 AF XY: 0.00125 AC XY: 911 AN XY: 727240

Gnomad4 AFR exome AF: 0.000777

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.000711

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.00126

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152272 Hom.: 1 Cov.: 32 AF XY: 0.00106 AC XY: 79 AN XY: 74456

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00106 Hom.: 0

Bravo AF: 0.00109

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00169

EpiControl AF: 0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

LRRC4C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.46
Dann	Benign	0.50

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: rs142620688; hg19: chr11-40136163; COSMIC: COSV53432319; COSMIC: COSV53432319;