Genetic Variant NM_002319.5:c.1898G>C (chr7-100575261-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002319.5(LRCH4):c.1898G>C(p.Arg633Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,426,916 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R633Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

LRCH4
NM_002319.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.150

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108628124).

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.1898G>C	p.Arg633Pro	missense	Exon 18 of 18	NP_002310.2
	LRCH4	NM_001289934.2		c.1854+444G>C		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.1898G>C	p.Arg633Pro	missense	Exon 18 of 18	ENSP00000309689.6	O75427
LRCH4	ENST00000877649.1		c.1910G>C	p.Arg637Pro	missense	Exon 18 of 18	ENSP00000547708.1
LRCH4	ENST00000965051.1		c.1895G>C	p.Arg632Pro	missense	Exon 18 of 18	ENSP00000635110.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1426916

Hom.:

Cov.:

AF XY:

0.00000991

AC XY:

AN XY:

706474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32898

American (AMR)

AF:

0.00

AC:

AN:

38494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25382

East Asian (EAS)

AF:

0.00

AC:

AN:

38310

South Asian (SAS)

AF:

0.000133

AC:

AN:

82950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

1093578

Other (OTH)

AF:

0.0000170

AC:

AN:

58914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.9

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.69

M_CAP

Benign

0.018

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

-0.15

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.1

REVEL

Benign

0.10

Sift

Uncertain

0.012

Sift4G

Benign

0.11

Polyphen

0.093

Vest4

0.14

MutPred

0.58

Loss of MoRF binding (P = 0.0016)

MVP

0.32

MPC

0.42

ClinPred

0.34

GERP RS

2.6

Varity_R

0.45

gMVP

0.75

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over