Genetic Variant LRRC24:p.Met424Ile (chr8-144522745-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001024678.4(LRRC24):c.1272G>C(p.Met424Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,587,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 1 hom. )

Consequence

LRRC24
NM_001024678.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

Publications

0 publications found

Variant links:

Genes affected

LRRC24 (HGNC:28947): (leucine rich repeat containing 24) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LRRC24 links:

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

LRRC14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17013398).

BS2

High AC in GnomAd4 at 43 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024678.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC24	NM_001024678.4	MANE Select	c.1272G>C	p.Met424Ile	missense	Exon 5 of 5	NP_001019849.2	Q50LG9
LRRC14	NM_014665.4	MANE Select	c.*1267C>G		3_prime_UTR	Exon 4 of 4	NP_055480.1	Q15048
LRRC14	NM_001272036.2		c.*1267C>G		3_prime_UTR	Exon 5 of 5	NP_001258965.1	Q15048

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC24	ENST00000529415.7	TSL:1 MANE Select	c.1272G>C	p.Met424Ile	missense	Exon 5 of 5	ENSP00000434849.1	Q50LG9
LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*1267C>G		3_prime_UTR	Exon 4 of 4	ENSP00000292524.1	Q15048
LRRC24	ENST00000533758.1	TSL:5	c.1263G>C	p.Met421Ile	missense	Exon 5 of 5	ENSP00000435653.1	G3V1D8

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000559

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000274

AC:

AN:

197274

AF XY:

0.000274

show subpopulations

Gnomad AFR exome

AF:

0.000105

Gnomad AMR exome

AF:

0.000131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000553

Gnomad OTH exome

AF:

0.000398

GnomAD4 exome

AF:

0.000640

AC:

919

AN:

1435330

Hom.:

Cov.:

AF XY:

0.000617

AC XY:

440

AN XY:

712568

show subpopulations

African (AFR)

AF:

0.0000629

AC:

AN:

31810

American (AMR)

AF:

0.0000955

AC:

AN:

41870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25574

East Asian (EAS)

AF:

0.00

AC:

AN:

37718

South Asian (SAS)

AF:

0.00

AC:

AN:

82988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5484

European-Non Finnish (NFE)

AF:

0.000806

AC:

887

AN:

1101032

Other (OTH)

AF:

0.000439

AC:

AN:

59242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

114

172

229

286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.000282

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41594

American (AMR)

AF:

0.000131

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.000425

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000466

AC:

ESP6500EA

AF:

0.000236

AC:

ExAC

AF:

0.000161

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

Uncertain

0.35

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.026

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

3.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.2

REVEL

Benign

0.049

Sift

Uncertain

0.019

Sift4G

Pathogenic

0.0

Polyphen

0.67

Vest4

0.42

MutPred

0.44

Loss of catalytic residue at M424 (P = 0.0602)

MVP

0.36

MPC

0.58

ClinPred

0.20

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.41

gMVP

0.34

Mutation Taster

=74/26

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over