NM_001024678.4:c.1487G>C

Variant names:

• chr8-144522530-C-G
• NM_001024678.4:c.1487G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 13/21 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. G496R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: LRRC24 NM_001024678.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13626677).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC24	NM_001024678.4	c.1487G>C	p.Gly496Ala	missense_variant	Exon 5 of 5	ENST00000529415.7	NP_001019849.2
LRRC14	NM_014665.4	c.*1052C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000292524.6	NP_055480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC24	ENST00000529415.7	c.1487G>C	p.Gly496Ala	missense_variant	Exon 5 of 5	1	NM_001024678.4	ENSP00000434849.1
LRRC14	ENST00000292524.6	c.*1052C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_014665.4	ENSP00000292524.1
LRRC24	ENST00000533758.1	c.1478G>C	p.Gly493Ala	missense_variant	Exon 5 of 5	5		ENSP00000435653.1
LRRC14	ENST00000528528.1	n.-52C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000658 AC: 9 AN: 1368736 Hom.: 0 Cov.: 29 AF XY: 0.00000888 AC XY: 6 AN XY: 675788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000842

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1487G>C (p.G496A) alteration is located in exon 5 (coding exon 4) of the LRRC24 gene. This alteration results from a G to C substitution at nucleotide position 1487, causing the glycine (G) at amino acid position 496 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.55
DEOGEN2	Benign	0.0069	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.50	T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.10
Sift	Benign	0.72	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.52	P;P
Vest4		0.32
MutPred		0.10		Loss of catalytic residue at G496 (P = 0.0477);.;
MVP		0.63
MPC		0.60
ClinPred		0.24	T
GERP RS		3.8
Varity_R		0.050
gMVP		0.065

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145747914;