rs201047365

Variant names:

• chr15-34359248-G-C
• rs201047365
• NM_153613.3:c.1454C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-34359248-G-C
• chr15-34359248-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_153613.3(LPCAT4):​c.1454C>G​(p.Thr485Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000212 in 1,563,688 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.00021 (2 hom.)
• Consequence: LPCAT4 NM_153613.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21
• Publications: 2 publications found

Genes affected

LPCAT4 (HGNC:30059): (lysophosphatidylcholine acyltransferase 4) Members of the 1-acylglycerol-3-phosphate O-acyltransferase (EC 2.3.1.51) family, such as AGPAT7, catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), a precursor in the biosynthesis of all glycerolipids. Both LPA and PA are involved in signal transduction (Ye et al., 2005 [PubMed 16243729]).[supplied by OMIM, May 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03060332).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153613.3. 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
	LPCAT4	NM_153613.3	MANE Select	c.1454C>G	p.Thr485Ser	missense	Exon 14 of 14	NP_705841.2	Q643R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT4	ENST00000314891.11	TSL:1 MANE Select	c.1454C>G	p.Thr485Ser	missense	Exon 14 of 14	ENSP00000317300.6	Q643R3
	LPCAT4	ENST00000927810.1		c.1451C>G	p.Thr484Ser	missense	Exon 14 of 14	ENSP00000597869.1
	LPCAT4	ENST00000954576.1		c.1445C>G	p.Thr482Ser	missense	Exon 14 of 14	ENSP00000624635.1

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 34 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000260 AC: 44 AN: 169062 AF XY: 0.000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.000236

Gnomad EAS exome AF: 0.0000789

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000307

Gnomad OTH exome AF: 0.000650

GnomAD4 exome AF: 0.000210 AC: 297 AN: 1411480 Hom.: 2 Cov.: 31 AF XY: 0.000260 AC XY: 181 AN XY: 697414

African (AFR) AF: 0.0000308 AC: 1 AN: 32426

American (AMR) AF: 0.000109 AC: 4 AN: 36812

Ashkenazi Jewish (ASJ) AF: 0.000120 AC: 3 AN: 25088

East Asian (EAS) AF: 0.00 AC: 0 AN: 37168

South Asian (SAS) AF: 0.000824 AC: 66 AN: 80124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50258

Middle Eastern (MID) AF: 0.00211 AC: 12 AN: 5690

European-Non Finnish (NFE) AF: 0.000185 AC: 201 AN: 1085402

Other (OTH) AF: 0.000171 AC: 10 AN: 58512

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41524

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

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000254 Hom.: 0

Bravo AF: 0.000170

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000169 AC: 20

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.045
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.21
Sift	Benign	0.33	T
Sift4G	Benign	0.19	T
Polyphen		0.012	B
Vest4		0.14
MutPred		0.24		Gain of ubiquitination at K481 (P = 0.0609)
MVP		0.34
MPC		0.010
ClinPred		0.012	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.15
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201047365; hg19: chr15-34651449;