11-10563963-G-T

Variant names:

• chr11-10563963-G-T
• rs949259277
• NM_006691.4:c.374C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006691.4(LYVE1):​c.374C>A​(p.Ala125Glu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: -1.97
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053865463).

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.374C>A	p.Ala125Glu	missense	Exon 3 of 6	NP_006682.2
	IRAG1-AS1	NR_034093.2		n.307+22421G>T		intron	N/A
	IRAG1-AS1	NR_034094.2		n.307+22421G>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.374C>A	p.Ala125Glu	missense	Exon 3 of 6	ENSP00000256178.3	Q9Y5Y7
	LYVE1	ENST00000860862.1		c.374C>A	p.Ala125Glu	missense	Exon 3 of 5	ENSP00000530921.1
	LYVE1	ENST00000529598.1	TSL:2	c.86-3163C>A		intron	N/A	ENSP00000436016.1	F2Z296

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.27
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.080
DANN	Benign	0.54
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.068
Sift	Benign	0.81	T
Sift4G	Benign	0.56	T
Polyphen		0.014	B
Vest4		0.23
MutPred		0.56		Gain of sheet (P = 0.039)
MVP		0.048
MPC		0.096
ClinPred		0.057	T
GERP RS		-4.8
Varity_R		0.089
gMVP		0.49
Mutation Taster		=99/1	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: rs949259277; hg19: chr11-10585510;