8-144522696-C-A

Variant names:

• chr8-144522696-C-A
• rs781048518
• NM_001024678.4:c.1321G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001024678.4(LRRC24):​c.1321G>T​(p.Glu441*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRRC24 NM_001024678.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1321G>T	p.Glu441*	stop_gained	Exon 5 of 5	NP_001019849.2	Q50LG9
	LRRC14	NM_014665.4	MANE Select	c.*1218C>A		3_prime_UTR	Exon 4 of 4	NP_055480.1	Q15048
	LRRC14	NM_001272036.2		c.*1218C>A		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.1321G>T	p.Glu441*	stop_gained	Exon 5 of 5	ENSP00000434849.1	Q50LG9
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*1218C>A		3_prime_UTR	Exon 4 of 4	ENSP00000292524.1	Q15048
	LRRC24	ENST00000533758.1	TSL:5	c.1312G>T	p.Glu438*	stop_gained	Exon 5 of 5	ENSP00000435653.1	G3V1D8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442678 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 716654

African (AFR) AF: 0.00 AC: 0 AN: 32236

American (AMR) AF: 0.00 AC: 0 AN: 42832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 38298

South Asian (SAS) AF: 0.00 AC: 0 AN: 83776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103892

Other (OTH) AF: 0.00 AC: 0 AN: 59528

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.86
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.92	D
PhyloP100		1.8
Vest4		0.084
GERP RS		4.9
Mutation Taster		=18/182	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs781048518; hg19: chr8-145748080;