rs2136675

chr6-160475399-A-Cchr6-160475399-A-G

Variant summary

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

The NR_028093.1(LPAL2):n.1505+1730T>G 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 0.274 in 152,000 control chromosomes in the GnomAD database, including 6,433 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 0.27 (6433 hom., cov: 32)
• Consequence: LPAL2 NR_028093.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPAL2	NR_028093.1	n.1505+1730T>G		intron_variant, non_coding_transcript_variant
LPAL2	NR_028092.1	n.1505+1730T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAL2	ENST00000335388.5	n.1505+1730T>G		intron_variant, non_coding_transcript_variant		1
LPAL2	ENST00000435757.6	n.1504+1731T>G		intron_variant, non_coding_transcript_variant		1
LPAL2	ENST00000454031.6	n.1572+1730T>G		intron_variant, non_coding_transcript_variant
LPAL2	ENST00000606083.1	n.67+1730T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41628 AN: 151882 Hom.: 6425 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.274 AC: 41660 AN: 152000 Hom.: 6433 Cov.: 32 AF XY: 0.279 AC XY: 20713 AN XY: 74288

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.310

Alfa AF: 0.299 Hom.: 6608

Bravo AF: 0.277

Asia WGS AF: 0.426 AC: 1479 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.3
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: rs2136675; hg19: chr6-160896431;