NM_006691.4:c.691G>A

Variant names:

• chr11-10560507-C-T
• rs1029365465
• NM_006691.4:c.691G>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.691G>A​(p.Ala231Thr) 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. 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. A231S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYVE1 NM_006691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• 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=0.04163584).

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.691G>A	p.Ala231Thr	missense	Exon 4 of 6	NP_006682.2
	IRAG1-AS1	NR_034093.2		n.307+18965C>T		intron	N/A
	IRAG1-AS1	NR_034094.2		n.307+18965C>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.691G>A	p.Ala231Thr	missense	Exon 4 of 6	ENSP00000256178.3	Q9Y5Y7
	LYVE1	ENST00000529598.1	TSL:2	c.379G>A	p.Ala127Thr	missense	Exon 2 of 4	ENSP00000436016.1	F2Z296
	LYVE1	ENST00000860862.1		c.398-613G>A		intron	N/A	ENSP00000530921.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.4
DANN	Benign	0.93
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.26
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.027
Sift	Benign	0.11	T
Sift4G	Uncertain	0.050	T
Polyphen		0.094	B
Vest4		0.028
MutPred		0.19		Gain of glycosylation at A231 (P = 0.0303)
MVP		0.11
MPC		0.074
ClinPred		0.060	T
GERP RS		0.43
Varity_R		0.037
gMVP		0.23
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

dbSNP: rs1029365465; hg19: chr11-10582054;