rs147788904

Variant names:

• chr11-10564026-G-A
• rs147788904
• NM_006691.4:c.311C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006691.4(LYVE1):​c.311C>T​(p.Pro104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 1,614,152 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (6 hom.)
• Consequence: LYVE1 NM_006691.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011845171).
• BP6: Variant 11-10564026-G-A is Benign according to our data. Variant chr11-10564026-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.311C>T	p.Pro104Leu	missense	Exon 3 of 6	NP_006682.2
	IRAG1-AS1	NR_034093.2		n.307+22484G>A		intron	N/A
	IRAG1-AS1	NR_034094.2		n.307+22484G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYVE1	ENST00000256178.8	TSL:1 MANE Select	c.311C>T	p.Pro104Leu	missense	Exon 3 of 6	ENSP00000256178.3	Q9Y5Y7
	LYVE1	ENST00000860862.1		c.311C>T	p.Pro104Leu	missense	Exon 3 of 5	ENSP00000530921.1
	LYVE1	ENST00000529598.1	TSL:2	c.86-3226C>T		intron	N/A	ENSP00000436016.1	F2Z296

Frequencies

GnomAD3 genomes AF: 0.000999 AC: 152 AN: 152144 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00127 AC: 319 AN: 251292 AF XY: 0.00135

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0121

Gnomad NFE exome AF: 0.000414

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000524 AC: 766 AN: 1461890 Hom.: 6 Cov.: 32 AF XY: 0.000531 AC XY: 386 AN XY: 727246

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

American (AMR) AF: 0.000134 AC: 6 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0107 AC: 569 AN: 53420

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

European-Non Finnish (NFE) AF: 0.000153 AC: 170 AN: 1112012

Other (OTH) AF: 0.000348 AC: 21 AN: 60396

GnomAD4 genome AF: 0.000998 AC: 152 AN: 152262 Hom.: 2 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74448

African (AFR) AF: 0.0000481 AC: 2 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0107 AC: 113 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000374 Hom.: 0

Bravo AF: 0.000155

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000947 AC: 115

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.91	P
Vest4		0.37
MVP		0.43
MPC		0.38
ClinPred		0.18	T
GERP RS		5.3
Varity_R		0.15
gMVP		0.35
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: rs147788904; hg19: chr11-10585573;