rs12214416

Positions:

• chr6-160489485-T-A

Variant summary

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

The NR_028093.1(LPAL2):​n.509-2053A>T 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 0.0393 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 NR_028093.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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=-0.91).
• 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/exons	MANE	UniProt
LPAL2	NR_028093.1	n.509-2053A>T		intron_variant, non_coding_transcript_variant
LPAL2	NR_028092.1	n.509-2053A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAL2	ENST00000335388.5	n.509-2053A>T		intron_variant, non_coding_transcript_variant		1
LPAL2	ENST00000435757.6	n.509-2053A>T		intron_variant, non_coding_transcript_variant		1
LPAL2	ENST00000454031.6	n.549+1878A>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0476

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0488

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12214416; hg19: chr6-160910517;