chr14-49607889-G-C

Variant names:

• chr14-49607889-G-C
• NM_152329.4:c.772G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152329.4(LRR1):​c.772G>C​(p.Asp258His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,408 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRR1 NM_152329.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.76

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRR1	NM_152329.4	c.772G>C	p.Asp258His	missense_variant	Exon 3 of 4	ENST00000298288.11	NP_689542.2
LRR1	NM_203467.2	c.282+5421G>C		intron_variant	Intron 2 of 2		NP_982292.1
LRR1	NR_037792.2	n.920G>C		non_coding_transcript_exon_variant	Exon 4 of 6
LRR1	NR_037793.2	n.961G>C		non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRR1	ENST00000298288.11	c.772G>C	p.Asp258His	missense_variant	Exon 3 of 4	1	NM_152329.4	ENSP00000298288.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460408 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726312

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00093	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.37	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.26
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.36		Gain of catalytic residue at E260 (P = 0.0071);
MVP		0.60
MPC		0.20
ClinPred		0.80	D
GERP RS		5.1
Varity_R		0.091
gMVP		0.73

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: chr14-50074607;