rs12214416

Variant names:

• chr6-160489485-T-A
• rs12214416
• ENST00000335388.5:n.509-2053A>T

Variant summary

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

The ENST00000335388.5(LPAL2):​n.509-2053A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 152,280 control chromosomes in the GnomAD database, including 158 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 0.039 (158 hom., cov: 33)
• Consequence: LPAL2 ENST00000335388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAL2	NR_028092.1	n.509-2053A>T		intron_variant	Intron 3 of 9
LPAL2	NR_028093.1	n.509-2053A>T		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAL2	ENST00000335388.5	n.509-2053A>T		intron_variant	Intron 3 of 9	1
LPAL2	ENST00000435757.6	n.509-2053A>T		intron_variant	Intron 3 of 9	1
LPAL2	ENST00000454031.6	n.549+1878A>T		intron_variant	Intron 4 of 16	6

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5985 AN: 152162 Hom.: 158 Cov.: 33

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0393 AC: 5982 AN: 152280 Hom.: 158 Cov.: 33 AF XY: 0.0409 AC XY: 3044 AN XY: 74460

African (AFR) AF: 0.0101 AC: 421 AN: 41578

American (AMR) AF: 0.0710 AC: 1084 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.0318 AC: 165 AN: 5184

South Asian (SAS) AF: 0.0476 AC: 230 AN: 4828

European-Finnish (FIN) AF: 0.0518 AC: 550 AN: 10610

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0469 AC: 3187 AN: 68020

Other (OTH) AF: 0.0488 AC: 103 AN: 2110

Alfa AF: 0.0408 Hom.: 17

Bravo AF: 0.0391

Asia WGS AF: 0.0460 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.34
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs12214416; hg19: chr6-160910517;