ENST00000335388.5:n.850+407T>C

Variant names:

• chr6-160485408-A-G
• rs2941382
• ENST00000335388.5:n.850+407T>C

Variant summary

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

The ENST00000335388.5(LPAL2):​n.850+407T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 151,794 control chromosomes in the GnomAD database, including 56,888 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 0.86 (56888 hom., cov: 31)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.850+407T>C		intron_variant	Intron 5 of 9
LPAL2	NR_028093.1	n.850+407T>C		intron_variant	Intron 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.850+407T>C		intron_variant	Intron 5 of 9	1
LPAL2	ENST00000435757.6	n.850+407T>C		intron_variant	Intron 5 of 9	1
LPAL2	ENST00000454031.6	n.891+407T>C		intron_variant	Intron 6 of 16	6

Frequencies

GnomAD3 genomes AF: 0.863 AC: 130825 AN: 151676 Hom.: 56824 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.863 AC: 130951 AN: 151794 Hom.: 56888 Cov.: 31 AF XY: 0.863 AC XY: 64019 AN XY: 74164

African (AFR) AF: 0.950 AC: 39120 AN: 41174

American (AMR) AF: 0.821 AC: 12545 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2871 AN: 3468

East Asian (EAS) AF: 0.996 AC: 5144 AN: 5166

South Asian (SAS) AF: 0.897 AC: 4317 AN: 4812

European-Finnish (FIN) AF: 0.827 AC: 8762 AN: 10590

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55277 AN: 68004

Other (OTH) AF: 0.876 AC: 1840 AN: 2100

Alfa AF: 0.833 Hom.: 32517

Bravo AF: 0.865

Asia WGS AF: 0.947 AC: 3291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15
DANN	Benign	0.40
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs2941382; hg19: chr6-160906440;