Genetic Variant LPCAT1:p.Ala480Gly (chr5-1463817-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024830.5(LPCAT1):c.1439C>G(p.Ala480Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

LPCAT1
NM_024830.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.65

Publications

6 publications found

Variant links:

Genes affected

LPCAT1 (HGNC:25718): (lysophosphatidylcholine acyltransferase 1) This gene encodes a member of the 1-acyl-sn-glycerol-3-phosphate acyltransferase family of proteins. The encoded enzyme plays a role in phospholipid metabolism, specifically in the conversion of lysophosphatidylcholine to phosphatidylcholine in the presence of acyl-CoA. This process is important in the synthesis of lung surfactant and platelet-activating factor (PAF). Elevated expression of this gene may contribute to the progression of oral squamous cell, prostate, breast, and other human cancers. [provided by RefSeq, Sep 2016]

LPCAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013639092).

BP6

Variant 5-1463817-G-C is Benign according to our data. Variant chr5-1463817-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2655277.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024830.5. 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
	LPCAT1	NM_024830.5	MANE Select	c.1439C>G	p.Ala480Gly	missense	Exon 14 of 14	NP_079106.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LPCAT1	ENST00000283415.4	TSL:1 MANE Select	c.1439C>G	p.Ala480Gly	missense	Exon 14 of 14	ENSP00000283415.3	Q8NF37
LPCAT1	ENST00000934191.1		c.1535C>G	p.Ala512Gly	missense	Exon 15 of 15	ENSP00000604250.1
LPCAT1	ENST00000934189.1		c.1526C>G	p.Ala509Gly	missense	Exon 15 of 15	ENSP00000604248.1

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

156

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00145

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000896

AC:

225

AN:

251172

AF XY:

0.000869

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000898

AC:

1313

AN:

1461804

Hom.:

Cov.:

AF XY:

0.000930

AC XY:

676

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33478

American (AMR)

AF:

0.00121

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00203

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000336

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000978

AC:

1087

AN:

1111956

Other (OTH)

AF:

0.00114

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

131

197

262

328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<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

AF:

0.00102

AC:

156

AN:

152368

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000264

AC:

AN:

41594

American (AMR)

AF:

0.00203

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00146

AC:

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.000979

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.000840

AC:

102

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00154

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.56

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.81

M_CAP

Benign

0.061

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.7

PhyloP100

2.7

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.28

Sift

Benign

0.033

Sift4G

Uncertain

0.013

Polyphen

0.049

Vest4

0.36

MVP

0.85

MPC

1.0

ClinPred

0.044

GERP RS

2.4

Varity_R

0.39

gMVP

0.55

Mutation Taster

=80/20

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over