Genetic Variant NM_006691.4:c.691G>C (chr11-10560507-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006691.4(LYVE1):c.691G>C(p.Ala231Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

LYVE1
NM_006691.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.256

Publications

0 publications found

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 was made for transcript

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=0.05158326).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LYVE1	NM_006691.4	MANE Select	c.691G>C	p.Ala231Pro	missense	Exon 4 of 6	NP_006682.2
IRAG1-AS1	NR_034093.2		n.307+18965C>G		intron	N/A
IRAG1-AS1	NR_034094.2		n.307+18965C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYVE1	ENST00000256178.8	TSL:1 MANE Select	c.691G>C	p.Ala231Pro	missense	Exon 4 of 6	ENSP00000256178.3	Q9Y5Y7
LYVE1	ENST00000529598.1	TSL:2	c.379G>C	p.Ala127Pro	missense	Exon 2 of 4	ENSP00000436016.1	F2Z296
LYVE1	ENST00000860862.1		c.398-613G>C		intron	N/A	ENSP00000530921.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

242276

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454194

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722576

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33302

American (AMR)

AF:

0.00

AC:

AN:

44022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39600

South Asian (SAS)

AF:

0.00

AC:

AN:

85388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1107206

Other (OTH)

AF:

0.00

AC:

AN:

60066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.15

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.53

M_CAP

Benign

0.0096

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

-0.26

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.79

REVEL

Benign

0.025

Sift

Benign

0.13

Sift4G

Uncertain

0.015

Polyphen

0.0010

Vest4

0.064

MutPred

0.28

Gain of loop (P = 0.024)

MVP

0.15

MPC

0.098

ClinPred

0.024

GERP RS

0.43

Varity_R

0.10

gMVP

0.40

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over