NM_006691.4:c.614T>A

Variant names:

• chr11-10560584-A-T
• NM_006691.4:c.614T>A

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.614T>A​(p.Val205Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V205A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYVE1 NM_006691.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.628
• 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=0.09117749).

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.614T>A	p.Val205Asp	missense	Exon 4 of 6	NP_006682.2
	IRAG1-AS1	NR_034093.2		n.307+19042A>T		intron	N/A
	IRAG1-AS1	NR_034094.2		n.307+19042A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYVE1	ENST00000256178.8	TSL:1 MANE Select	c.614T>A	p.Val205Asp	missense	Exon 4 of 6	ENSP00000256178.3	Q9Y5Y7
	LYVE1	ENST00000529598.1	TSL:2	c.302T>A	p.Val101Asp	missense	Exon 2 of 4	ENSP00000436016.1	F2Z296
	LYVE1	ENST00000860862.1		c.398-690T>A		intron	N/A	ENSP00000530921.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.9
DANN	Benign	0.84
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.63
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.041
Sift	Benign	0.14	T
Sift4G	Uncertain	0.046	D
Polyphen		0.45	P
Vest4		0.23
MutPred		0.24		Loss of sheet (P = 0.0228)
MVP		0.27
MPC		0.29
ClinPred		0.18	T
GERP RS		0.47
Varity_R		0.15
gMVP		0.64
Mutation Taster		=94/6	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

hg19: chr11-10582131;