6-160490876-C-T

Variant names:

• chr6-160490876-C-T
• rs9365166
• ENST00000335388.5:n.508+1905G>A

Variant summary

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

The ENST00000335388.5(LPAL2):​n.508+1905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,940 control chromosomes in the GnomAD database, including 16,758 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 (16758 hom., cov: 32)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.508+1905G>A		intron_variant	Intron 3 of 9
LPAL2	NR_028093.1	n.508+1905G>A		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.508+1905G>A		intron_variant	Intron 3 of 9	1
LPAL2	ENST00000435757.6	n.508+1905G>A		intron_variant	Intron 3 of 9	1
LPAL2	ENST00000719164.1	n.1095G>A		non_coding_transcript_exon_variant	Exon 4 of 4
LPAL2	ENST00000454031.6	n.549+487G>A		intron_variant	Intron 4 of 16	6

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67141 AN: 151822 Hom.: 16737 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.442 AC: 67189 AN: 151940 Hom.: 16758 Cov.: 32 AF XY: 0.450 AC XY: 33391 AN XY: 74216

African (AFR) AF: 0.221 AC: 9150 AN: 41462

American (AMR) AF: 0.559 AC: 8522 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1740 AN: 3468

East Asian (EAS) AF: 0.880 AC: 4545 AN: 5162

South Asian (SAS) AF: 0.661 AC: 3179 AN: 4806

European-Finnish (FIN) AF: 0.482 AC: 5073 AN: 10530

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

European-Non Finnish (NFE) AF: 0.491 AC: 33337 AN: 67942

Other (OTH) AF: 0.493 AC: 1040 AN: 2110

Alfa AF: 0.479 Hom.: 4118

Bravo AF: 0.440

Asia WGS AF: 0.753 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.75
PhyloP100		-0.66

Splicing

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

Other links and lift over

dbSNP: rs9365166; hg19: chr6-160911908; COSMIC: COSV59017749;