rs6415084

chr6-160559298-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005577.4(LPA):c.4632-1727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,116 control chromosomes in the GnomAD database, including 25,635 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 0.57 (25635 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

Genes affected

LPA (HGNC:6667): (lipoprotein(a)) The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.4632-1727A>G		intron_variant		ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.4632-1727A>G		intron_variant		1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87354 AN: 151998 Hom.: 25599 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.575 AC: 87438 AN: 152116 Hom.: 25635 Cov.: 33 AF XY: 0.584 AC XY: 43397 AN XY: 74344

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.540

Alfa AF: 0.530 Hom.: 24466

Bravo AF: 0.577

Asia WGS AF: 0.788 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	2.5
Dann	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6415084; hg19: chr6-160980330;