Genetic Variant NM_001024678.4:c.1487G>C (chr8-144522530-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.1487G>C(p.Gly496Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 1,368,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G496E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

LRRC24
NM_001024678.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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:

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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=0.13626677).

BS2

High AC in GnomAdExome4 at 9 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.1487G>C	p.Gly496Ala	missense	Exon 5 of 5	NP_001019849.2	Q50LG9
LRRC14	NM_014665.4	MANE Select	c.*1052C>G		3_prime_UTR	Exon 4 of 4	NP_055480.1	Q15048
LRRC14	NM_001272036.2		c.*1052C>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.1487G>C	p.Gly496Ala	missense	Exon 5 of 5	ENSP00000434849.1	Q50LG9
LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*1052C>G		3_prime_UTR	Exon 4 of 4	ENSP00000292524.1	Q15048
LRRC24	ENST00000533758.1	TSL:5	c.1478G>C	p.Gly493Ala	missense	Exon 5 of 5	ENSP00000435653.1	G3V1D8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000658

AC:

AN:

1368736

Hom.:

Cov.:

AF XY:

0.00000888

AC XY:

AN XY:

675788

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28452

American (AMR)

AF:

0.00

AC:

AN:

31670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23766

East Asian (EAS)

AF:

0.00

AC:

AN:

32126

South Asian (SAS)

AF:

0.00

AC:

AN:

76240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

0.00000842

AC:

AN:

1068642

Other (OTH)

AF:

0.00

AC:

AN:

56622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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.:

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

0.067

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

2.4

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.13

REVEL

Benign

0.10

Sift

Benign

0.72

Sift4G

Benign

1.0

Polyphen

0.52

Vest4

0.32

MutPred

0.10

Loss of catalytic residue at G496 (P = 0.0477)

MVP

0.63

MPC

0.60

ClinPred

0.24

GERP RS

3.8

Varity_R

0.050

gMVP

0.065

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

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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