6-160500534-T-G

Variant names:

• chr6-160500534-T-G
• rs9457930
• ENST00000335388.5:n.326+247A>C

Variant summary

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

The ENST00000335388.5(LPAL2):​n.326+247A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,018 control chromosomes in the GnomAD database, including 16,717 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 0.44 (16717 hom., cov: 32)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.326+247A>C		intron_variant	Intron 2 of 9
LPAL2	NR_028093.1	n.326+247A>C		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.326+247A>C		intron_variant	Intron 2 of 9	1
LPAL2	ENST00000435757.6	n.326+247A>C		intron_variant	Intron 2 of 9	1
LPAL2	ENST00000719163.1	n.711A>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66856 AN: 151900 Hom.: 16696 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.440 AC: 66904 AN: 152018 Hom.: 16717 Cov.: 32 AF XY: 0.448 AC XY: 33279 AN XY: 74304

African (AFR) AF: 0.213 AC: 8845 AN: 41482

American (AMR) AF: 0.558 AC: 8517 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3470

East Asian (EAS) AF: 0.882 AC: 4538 AN: 5148

South Asian (SAS) AF: 0.662 AC: 3189 AN: 4814

European-Finnish (FIN) AF: 0.481 AC: 5079 AN: 10554

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33358 AN: 67972

Other (OTH) AF: 0.490 AC: 1031 AN: 2106

Alfa AF: 0.476 Hom.: 26513

Bravo AF: 0.438

Asia WGS AF: 0.755 AC: 2624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.26
PhyloP100		-0.056

Splicing

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

Other links and lift over

dbSNP: rs9457930; hg19: chr6-160921566;