Variant 11-10559169-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000256178.8(LYVE1):c.911C>G(p.Pro304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

LYVE1
ENST00000256178.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.960

Variant links:

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]

LYVE1 links:

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

IRAG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06044382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYVE1	NM_006691.4 linkuse as main transcript	c.911C>G	p.Pro304Arg	missense_variant	6/6	ENST00000256178.8	NP_006682.2
IRAG1-AS1	NR_046374.1 linkuse as main transcript	n.307+17627G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYVE1	ENST00000256178.8 linkuse as main transcript	c.911C>G	p.Pro304Arg	missense_variant	6/6	1	NM_006691.4	ENSP00000256178	P1
IRAG1-AS1	ENST00000663840.1 linkuse as main transcript	n.285+17627G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000255

AC:

AN:

251432

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000536

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000250

AC:

366

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.000224

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000273

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000436

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.911C>G (p.P304R) alteration is located in exon 6 (coding exon 6) of the LYVE1 gene. This alteration results from a C to G substitution at nucleotide position 911, causing the proline (P) at amino acid position 304 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.9

N;D

REVEL

Benign

0.060

Sift

Benign

0.069

T;T

Sift4G

Uncertain

0.020

D;T

Polyphen

0.87

P;P

Vest4

0.10

MVP

0.50

MPC

0.18

ClinPred

0.056

GERP RS

4.1

Varity_R

0.043

gMVP

0.089

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over