11-10564054-C-G

Variant names:

• chr11-10564054-C-G
• rs139582089
• NM_006691.4:c.283G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006691.4(LYVE1):​c.283G>C​(p.Val95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V95M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LYVE1 NM_006691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992
• Publications: 0 publications found

Genes affected

LYVE1 (HGNC:14687): (lymphatic vessel endothelial hyaluronan receptor 1) This gene encodes a type I integral membrane glycoprotein. The encoded protein acts as a receptor and binds to both soluble and immobilized hyaluronan. This protein may function in lymphatic hyaluronan transport and have a role in tumor metastasis. [provided by RefSeq, Jul 2008]

IRAG1-AS1 (HGNC:43434): (IRAG1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14337444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006691.4. 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
	LYVE1	NM_006691.4	MANE Select	c.283G>C	p.Val95Leu	missense	Exon 3 of 6	NP_006682.2
	IRAG1-AS1	NR_034093.2		n.307+22512C>G		intron	N/A
	IRAG1-AS1	NR_034094.2		n.307+22512C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYVE1	ENST00000256178.8	TSL:1 MANE Select	c.283G>C	p.Val95Leu	missense	Exon 3 of 6	ENSP00000256178.3	Q9Y5Y7
	LYVE1	ENST00000860862.1		c.283G>C	p.Val95Leu	missense	Exon 3 of 5	ENSP00000530921.1
	LYVE1	ENST00000529598.1	TSL:2	c.86-3254G>C		intron	N/A	ENSP00000436016.1	F2Z296

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.027
DANN	Benign	0.74
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.99
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.043
Sift	Benign	0.27	T
Sift4G	Benign	0.52	T
Polyphen		0.0080	B
Vest4		0.18
MutPred		0.73		Gain of sheet (P = 0.0827)
MVP		0.20
MPC		0.085
ClinPred		0.23	T
GERP RS		-11
Varity_R		0.073
gMVP		0.48
Mutation Taster		=92/8	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: rs139582089; hg19: chr11-10585601;