rs55730499

Variant names:

• chr6-160584578-C-T
• rs55730499
• NM_005577.4:c.4289+468G>A

Variant summary

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

The NM_005577.4(LPA):​c.4289+468G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,048 control chromosomes in the GnomAD database, including 215 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 0.044 (215 hom., cov: 31)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 84 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005577.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	NM_005577.4	MANE Select	c.4289+468G>A		intron	N/A	NP_005568.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	ENST00000316300.10	TSL:1 MANE Select	c.4289+468G>A		intron	N/A	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6744 AN: 151930 Hom.: 214 Cov.: 31

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.0291

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0443 AC: 6742 AN: 152048 Hom.: 215 Cov.: 31 AF XY: 0.0413 AC XY: 3072 AN XY: 74328

African (AFR) AF: 0.0124 AC: 514 AN: 41490

American (AMR) AF: 0.0393 AC: 599 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3468

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5154

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4812

European-Finnish (FIN) AF: 0.0353 AC: 373 AN: 10568

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0711 AC: 4835 AN: 67992

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

Alfa AF: 0.0515 Hom.: 28

Bravo AF: 0.0425

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55730499; hg19: chr6-161005610; COSMIC: COSV60310350; COSMIC: COSV60310350;