Genetic Variant LRRC32:p.Arg614Leu (chr11-76659752-C-A) – 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_001128922.2(LRRC32):c.1841G>T(p.Arg614Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 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. R614H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRRC32
NM_001128922.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98

Publications

0 publications found

Variant links:

Genes affected

LRRC32 (HGNC:4161): (leucine rich repeat containing 32) This gene encodes a type I membrane protein which contains 20 leucine-rich repeats. Alterations in the chromosomal region 11q13-11q14 are involved in several pathologies. [provided by RefSeq, Jul 2008]

LRRC32 Gene-Disease associations (from GenCC):

cleft palate, proliferative retinopathy, and developmental delay
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LRRC32 links:

LRRC32-AS1 (HGNC:58233):

LRRC32-AS1 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=0.2334246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC32	NM_001128922.2	MANE Select	c.1841G>T	p.Arg614Leu	missense	Exon 3 of 3	NP_001122394.1	Q14392
LRRC32	NM_001370187.1		c.1841G>T	p.Arg614Leu	missense	Exon 3 of 4	NP_001357116.1	Q14392
LRRC32	NM_001370188.1		c.1841G>T	p.Arg614Leu	missense	Exon 3 of 4	NP_001357117.1	Q14392

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC32	ENST00000260061.9	TSL:1 MANE Select	c.1841G>T	p.Arg614Leu	missense	Exon 3 of 3	ENSP00000260061.5	Q14392
LRRC32	ENST00000407242.6	TSL:1	c.1841G>T	p.Arg614Leu	missense	Exon 3 of 3	ENSP00000384126.2	Q14392
LRRC32-AS1	ENST00000447519.2	TSL:1	n.260+58C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

0.0019

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

0.12

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

M_CAP

Benign

0.016

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

2.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.24

REVEL

Benign

0.13

Sift

Benign

0.13

Sift4G

Benign

0.34

Polyphen

0.96

Vest4

0.33

MutPred

0.41

Loss of sheet (P = 0.0228)

MVP

0.77

MPC

0.24

ClinPred

0.42

GERP RS

3.6

Varity_R

0.10

gMVP

0.76

Mutation Taster

=94/6

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over