Genetic Variant LRCH4:p.Gly646Glu (chr7-100575222-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002319.5(LRCH4):c.1937G>A(p.Gly646Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,608,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

LRCH4
NM_002319.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.298

Publications

0 publications found

Variant links:

Genes affected

LRCH4 (HGNC:6691): (leucine rich repeats and calponin homology domain containing 4) This gene encodes a protein that contains leucine-rich repeats (LRR) at its amino terminus and that is known to be involved in ligand binding. The carboxyl terminus may act as a membrane anchor. Identified structural elements suggest that the encoded protein resembles a receptor. [provided by RefSeq, Jul 2008]

LRCH4 links:

ENSG00000274272 (HGNC:):

ENSG00000274272 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09956542).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002319.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH4	NM_002319.5	MANE Select	c.1937G>A	p.Gly646Glu	missense	Exon 18 of 18	NP_002310.2
	LRCH4	NM_001289934.2		c.1854+483G>A		intron	N/A	NP_001276863.1	H7C5D9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRCH4	ENST00000310300.11	TSL:1 MANE Select	c.1937G>A	p.Gly646Glu	missense	Exon 18 of 18	ENSP00000309689.6	O75427
LRCH4	ENST00000877649.1		c.1949G>A	p.Gly650Glu	missense	Exon 18 of 18	ENSP00000547708.1
LRCH4	ENST00000965051.1		c.1934G>A	p.Gly645Glu	missense	Exon 18 of 18	ENSP00000635110.1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000426

AC:

AN:

234836

AF XY:

0.0000469

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000500

Gnomad NFE exome

AF:

0.0000574

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000113

AC:

164

AN:

1456504

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

724182

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

43728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.00

AC:

AN:

85630

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.000139

AC:

154

AN:

1109694

Other (OTH)

AF:

0.0000999

AC:

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000776

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000744

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.66

M_CAP

Benign

0.0074

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

PhyloP100

0.30

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

REVEL

Benign

0.096

Sift

Uncertain

0.0080

Sift4G

Benign

0.081

Polyphen

0.0010

Vest4

0.22

MVP

0.53

MPC

0.12

ClinPred

0.030

GERP RS

0.34

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Varity_R

0.094

gMVP

0.74

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over