rs3127569

Variant names:

• chr6-160496527-C-T
• rs3127569
• ENST00000335388.5:n.327-3565G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000335388.5(LPAL2):​n.327-3565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,054 control chromosomes in the GnomAD database, including 4,934 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4934 hom., cov: 32)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 7 publications found

Genes affected

LPAL2 (HGNC:):

LPAL2 (HGNC:21210): (lipoprotein(a) like 2 (pseudogene)) Apolipoprotein(a) is the distinguishing protein moiety of lipoprotein(a), of which elevated plasma levels are correlated with an increased risk of atherosclerosis. This gene is similar to the lipoprotein, Lp(a) gene, but all transcripts produced by this gene contain a truncated open reading frame and are candidates for nonsense-mediated decay. Consequently, this gene is considered to be a pseudogene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.327-3565G>A		intron_variant	Intron 2 of 9
LPAL2	NR_028093.1	n.327-3565G>A		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.327-3565G>A		intron_variant	Intron 2 of 9	1
LPAL2	ENST00000435757.6	n.327-3565G>A		intron_variant	Intron 2 of 9	1
LPAL2	ENST00000454031.6	n.210-3565G>A		intron_variant	Intron 2 of 16	6

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36976 AN: 151936 Hom.: 4937 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36966 AN: 152054 Hom.: 4934 Cov.: 32 AF XY: 0.242 AC XY: 18021 AN XY: 74316

African (AFR) AF: 0.159 AC: 6608 AN: 41506

American (AMR) AF: 0.184 AC: 2808 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1007 AN: 3466

East Asian (EAS) AF: 0.116 AC: 598 AN: 5174

South Asian (SAS) AF: 0.231 AC: 1111 AN: 4816

European-Finnish (FIN) AF: 0.344 AC: 3627 AN: 10538

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20336 AN: 67960

Other (OTH) AF: 0.241 AC: 509 AN: 2112

Alfa AF: 0.275 Hom.: 3766

Bravo AF: 0.224

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.47
PhyloP100		0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3127569; hg19: chr6-160917559;