chr14-49602430-C-G

Variant names:

• chr14-49602430-C-G
• NM_152329.4:c.244C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152329.4(LRR1):​c.244C>G​(p.Arg82Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,738 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: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRR1 NM_152329.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64

Genes affected

LRR1 (HGNC:19742): (leucine rich repeat protein 1) The protein encoded by this gene contains a leucine-rich repeat (LRR). It specifically interacts with TNFRSF9/4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily. Overexpression of this gene suppresses the activation of NF-kappa B induced by TNFRSF9 or TNF receptor-associated factor 2 (TRAF2), which suggests that this protein is a negative regulator of TNFRSF9-mediated signaling cascades. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRR1	NM_152329.4	c.244C>G	p.Arg82Gly	missense_variant	Exon 2 of 4	ENST00000298288.11	NP_689542.2
LRR1	NM_203467.2	c.244C>G	p.Arg82Gly	missense_variant	Exon 2 of 3		NP_982292.1
LRR1	NR_037792.2	n.325C>G		non_coding_transcript_exon_variant	Exon 2 of 6
LRR1	NR_037793.2	n.433C>G		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRR1	ENST00000298288.11	c.244C>G	p.Arg82Gly	missense_variant	Exon 2 of 4	1	NM_152329.4	ENSP00000298288.6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461738 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727186

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0060	D;T
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;D
Vest4		0.90
MutPred		0.45		Gain of catalytic residue at P86 (P = 5e-04);Gain of catalytic residue at P86 (P = 5e-04);
MVP		0.80
MPC		0.67
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.72
gMVP		0.78

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: chr14-50069148;