rs3123629

Variant names:

• chr6-160485054-G-A
• rs3123629
• ENST00000335388.5:n.850+761C>T

Variant summary

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

The ENST00000335388.5(LPAL2):​n.850+761C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,722 control chromosomes in the GnomAD database, including 6,207 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 0.28 (6207 hom., cov: 32)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 16 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.850+761C>T		intron_variant	Intron 5 of 9
LPAL2	NR_028093.1	n.850+761C>T		intron_variant	Intron 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.850+761C>T		intron_variant	Intron 5 of 9	1
LPAL2	ENST00000435757.6	n.850+761C>T		intron_variant	Intron 5 of 9	1
LPAL2	ENST00000454031.6	n.891+761C>T		intron_variant	Intron 6 of 16	6

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42008 AN: 151602 Hom.: 6207 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.277 AC: 42016 AN: 151722 Hom.: 6207 Cov.: 32 AF XY: 0.276 AC XY: 20431 AN XY: 74136

African (AFR) AF: 0.284 AC: 11702 AN: 41160

American (AMR) AF: 0.194 AC: 2963 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3466

East Asian (EAS) AF: 0.114 AC: 590 AN: 5160

South Asian (SAS) AF: 0.229 AC: 1103 AN: 4810

European-Finnish (FIN) AF: 0.342 AC: 3612 AN: 10570

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20134 AN: 67950

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.284 Hom.: 27017

Bravo AF: 0.263

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.91
DANN	Benign	0.36
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs3123629; hg19: chr6-160906086;