6-160482146-C-A

Variant names:

• chr6-160482146-C-A
• rs9355803
• ENST00000335388.5:n.1164+542G>T

Variant summary

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

The ENST00000335388.5(LPAL2):​n.1164+542G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,122 control chromosomes in the GnomAD database, including 2,504 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 0.17 (2504 hom., cov: 33)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.1164+542G>T		intron_variant	Intron 7 of 9
LPAL2	NR_028093.1	n.1164+542G>T		intron_variant	Intron 7 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.1164+542G>T		intron_variant	Intron 7 of 9	1
LPAL2	ENST00000435757.6	n.1164+542G>T		intron_variant	Intron 7 of 9	1
LPAL2	ENST00000454031.6	n.1231+516G>T		intron_variant	Intron 8 of 16	6

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25340 AN: 152006 Hom.: 2502 Cov.: 33

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.167 AC: 25356 AN: 152122 Hom.: 2504 Cov.: 33 AF XY: 0.169 AC XY: 12567 AN XY: 74358

African (AFR) AF: 0.0782 AC: 3247 AN: 41538

American (AMR) AF: 0.186 AC: 2836 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1755 AN: 5148

South Asian (SAS) AF: 0.264 AC: 1270 AN: 4818

European-Finnish (FIN) AF: 0.175 AC: 1853 AN: 10580

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13090 AN: 67988

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.186 Hom.: 5441

Bravo AF: 0.161

Asia WGS AF: 0.321 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.27
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs9355803; hg19: chr6-160903178; COSMIC: COSV59017714;