rs10945673

Variant names:

• chr6-160489867-C-T
• rs10945673
• ENST00000335388.5:n.509-2435G>A

Variant summary

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

The ENST00000335388.5(LPAL2):​n.509-2435G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,990 control chromosomes in the GnomAD database, including 2,453 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 0.16 (2453 hom., cov: 32)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.509-2435G>A		intron_variant	Intron 3 of 9
LPAL2	NR_028093.1	n.509-2435G>A		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.509-2435G>A		intron_variant	Intron 3 of 9	1
LPAL2	ENST00000435757.6	n.509-2435G>A		intron_variant	Intron 3 of 9	1
LPAL2	ENST00000454031.6	n.549+1496G>A		intron_variant	Intron 4 of 16	6
LPAL2	ENST00000719164.1	n.*98G>A		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24995 AN: 151870 Hom.: 2451 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.165 AC: 25007 AN: 151990 Hom.: 2453 Cov.: 32 AF XY: 0.167 AC XY: 12389 AN XY: 74268

African (AFR) AF: 0.0740 AC: 3068 AN: 41468

American (AMR) AF: 0.183 AC: 2786 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 612 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1264 AN: 4816

European-Finnish (FIN) AF: 0.177 AC: 1860 AN: 10532

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13007 AN: 67980

Other (OTH) AF: 0.171 AC: 360 AN: 2108

Alfa AF: 0.179 Hom.: 7500

Bravo AF: 0.158

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.029
DANN	Benign	0.55
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs10945673; hg19: chr6-160910899;