Variant 11-40115563-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001258419.2(LRRC4C):c.730C>T(p.His244Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

LRRC4C
NM_001258419.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

Variant links:

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]

LRRC4C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, LRRC4C

BS2

High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC4C	NM_001258419.2 linkuse as main transcript	c.730C>T	p.His244Tyr	missense_variant	7/7	ENST00000528697.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC4C	ENST00000528697.6 linkuse as main transcript	c.730C>T	p.His244Tyr	missense_variant	7/7	1	NM_001258419.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250856

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.730C>T (p.H244Y) alteration is located in exon 2 (coding exon 1) of the LRRC4C gene. This alteration results from a C to T substitution at nucleotide position 730, causing the histidine (H) at amino acid position 244 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.11

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.087

T;T;T;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.0073

MetaRNN

Uncertain

0.50

D;D;D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.93

L;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.2

N;.;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.032

D;.;D;D;D

Sift4G

Uncertain

0.039

D;D;D;D;D

Polyphen

0.76

P;P;P;P;P

Vest4

0.61

MVP

0.39

MPC

1.0

ClinPred

0.27

GERP RS

5.4

Varity_R

0.56

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over