rs10945673

Positions:

• chr6-160489867-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_028093.1(LPAL2):​n.509-2435G>A variant causes a intron, non coding transcript 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 NR_028093.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LPAL2	NR_028093.1	n.509-2435G>A		intron_variant, non_coding_transcript_variant
LPAL2	NR_028092.1	n.509-2435G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.509-2435G>A		intron_variant, non_coding_transcript_variant		1
LPAL2	ENST00000435757.6	n.509-2435G>A		intron_variant, non_coding_transcript_variant		1
LPAL2	ENST00000454031.6	n.549+1496G>A		intron_variant, non_coding_transcript_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

Gnomad4 AFR AF: 0.0740

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.171

Alfa AF: 0.187 Hom.: 5036

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10945673; hg19: chr6-160910899;