Genetic Variant LRCH4:p.Arg633Gln (chr7-100575261-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002319.5(LRCH4):c.1898G>A(p.Arg633Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,579,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R633W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

LRCH4
NM_002319.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053816557).

BP6

Variant 7-100575261-C-T is Benign according to our data. Variant chr7-100575261-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3119910.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A	p.Arg633Gln	missense	Exon 18 of 18	NP_002310.2
	LRCH4	NM_001289934.2		c.1854+444G>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.1898G>A	p.Arg633Gln	missense	Exon 18 of 18	ENSP00000309689.6	O75427
LRCH4	ENST00000877649.1		c.1910G>A	p.Arg637Gln	missense	Exon 18 of 18	ENSP00000547708.1
LRCH4	ENST00000965051.1		c.1895G>A	p.Arg632Gln	missense	Exon 18 of 18	ENSP00000635110.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000215

AC:

AN:

185798

AF XY:

0.0000398

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000260

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1426916

Hom.:

Cov.:

AF XY:

0.0000396

AC XY:

AN XY:

706474

show subpopulations

African (AFR)

AF:

0.0000912

AC:

AN:

32898

American (AMR)

AF:

0.0000260

AC:

AN:

38494

Ashkenazi Jewish (ASJ)

AF:

0.0000394

AC:

AN:

25382

East Asian (EAS)

AF:

0.00

AC:

AN:

38310

South Asian (SAS)

AF:

0.0000241

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:

0.0000366

AC:

AN:

1093578

Other (OTH)

AF:

0.00

AC:

AN:

58914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.0000329

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.064

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.023

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.62

M_CAP

Benign

0.0096

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-0.15

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.52

REVEL

Benign

0.028

Sift

Benign

0.26

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.098

MutPred

0.45

Loss of MoRF binding (P = 0.02)

MVP

0.24

MPC

0.094

ClinPred

0.051

GERP RS

2.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.031

gMVP

0.24

Mutation Taster

=94/6

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over