rs747941959

Variant names:

• chr8-144522531-C-G
• rs747941959
• NM_001024678.4:c.1486G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144522531-C-G
• chr8-144522531-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001024678.4(LRRC24):​c.1486G>C​(p.Gly496Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G496A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LRRC24 NM_001024678.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3079676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC24	NM_001024678.4	c.1486G>C	p.Gly496Arg	missense_variant	Exon 5 of 5	ENST00000529415.7	NP_001019849.2
LRRC14	NM_014665.4	c.*1053C>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.1486G>C	p.Gly496Arg	missense_variant	Exon 5 of 5	1	NM_001024678.4	ENSP00000434849.1
LRRC14	ENST00000292524.6	c.*1053C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_014665.4	ENSP00000292524.1
LRRC24	ENST00000533758.1	c.1477G>C	p.Gly493Arg	missense_variant	Exon 5 of 5	5		ENSP00000435653.1
LRRC14	ENST00000528528.1	n.-51C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0060	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.54	T;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.18
Sift	Benign	0.31	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.97	D;D
Vest4		0.36
MutPred		0.15		Gain of solvent accessibility (P = 0.0037);.;
MVP		0.75
MPC		1.1
ClinPred		0.65	D
GERP RS		2.8
Varity_R		0.060
gMVP		0.062

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

LitVar

Other links and lift over

dbSNP: rs747941959; hg19: chr8-145747915;