8-144522861-C-G

Variant names:

• chr8-144522861-C-G
• rs1383796094
• NM_001024678.4:c.1156G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001024678.4(LRRC24):​c.1156G>C​(p.Glu386Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000066 in 151,516 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 (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: LRRC24 NM_001024678.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3907049).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC24	NM_001024678.4	MANE Select	c.1156G>C	p.Glu386Gln	missense	Exon 5 of 5	NP_001019849.2	Q50LG9
	LRRC14	NM_014665.4	MANE Select	c.*1383C>G		3_prime_UTR	Exon 4 of 4	NP_055480.1	Q15048
	LRRC14	NM_001272036.2		c.*1383C>G		3_prime_UTR	Exon 5 of 5	NP_001258965.1	Q15048

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC24	ENST00000529415.7	TSL:1 MANE Select	c.1156G>C	p.Glu386Gln	missense	Exon 5 of 5	ENSP00000434849.1	Q50LG9
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*1383C>G		3_prime_UTR	Exon 4 of 4	ENSP00000292524.1	Q15048
	LRRC24	ENST00000533758.1	TSL:5	c.1147G>C	p.Glu383Gln	missense	Exon 5 of 5	ENSP00000435653.1	G3V1D8

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151516 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151516 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74020

African (AFR) AF: 0.0000242 AC: 1 AN: 41370

American (AMR) AF: 0.00 AC: 0 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67830

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	0.0048	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Uncertain	0.027	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.61	P
Vest4		0.37
MutPred		0.14		Gain of MoRF binding (P = 0.0873)
MVP		0.59
MPC		1.0
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.20
gMVP		0.55
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs1383796094; hg19: chr8-145748245;