rs146435333

Variant names:

• chr5-1470826-C-T
• rs146435333
• NM_024830.5:c.1278G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_024830.5(LPCAT1):​c.1278G>A​(p.Lys426Lys) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00078 in 1,613,440 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (4 hom.)
• Consequence: LPCAT1 NM_024830.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.5542
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.36
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 5-1470826-C-T is Benign according to our data. Variant chr5-1470826-C-T is described in ClinVar as Benign. ClinVar VariationId is 716860.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.1278G>A	p.Lys426Lys	splice_region synonymous	Exon 12 of 14	NP_079106.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT1	ENST00000283415.4	TSL:1 MANE Select	c.1278G>A	p.Lys426Lys	splice_region synonymous	Exon 12 of 14	ENSP00000283415.3	Q8NF37
	LPCAT1	ENST00000934191.1		c.1374G>A	p.Lys458Lys	splice_region synonymous	Exon 13 of 15	ENSP00000604250.1
	LPCAT1	ENST00000934189.1		c.1365G>A	p.Lys455Lys	splice_region synonymous	Exon 13 of 15	ENSP00000604248.1

Frequencies

GnomAD3 genomes AF: 0.00316 AC: 481 AN: 152236 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00116 AC: 290 AN: 250118 AF XY: 0.000835

Gnomad AFR exome AF: 0.0120

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000532 AC: 777 AN: 1461086 Hom.: 4 Cov.: 31 AF XY: 0.000494 AC XY: 359 AN XY: 726858

African (AFR) AF: 0.0117 AC: 393 AN: 33472

American (AMR) AF: 0.00150 AC: 67 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53104

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5766

European-Non Finnish (NFE) AF: 0.000186 AC: 207 AN: 1111706

Other (OTH) AF: 0.00133 AC: 80 AN: 60362

GnomAD4 genome AF: 0.00316 AC: 482 AN: 152354 Hom.: 1 Cov.: 33 AF XY: 0.00318 AC XY: 237 AN XY: 74504

African (AFR) AF: 0.0105 AC: 437 AN: 41584

American (AMR) AF: 0.00183 AC: 28 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68032

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00133 Hom.: 3

Bravo AF: 0.00403

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		4.4
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.55
dbscSNV1_RF	Benign	0.41
SpliceAI score (max)		0.010		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: rs146435333; hg19: chr5-1470941;