rs10755578

chr6-160548706-C-G

Variant summary

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

The NM_005577.4(LPA):c.4974-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,596,604 control chromosomes in the GnomAD database, including 174,330 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 0.42 (14018 hom., cov: 32)
  • Exomes 𝑓: 0.47 (160312 hom.)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.4974-47G>C		intron_variant		ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.4974-47G>C		intron_variant		1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64409 AN: 151850 Hom.: 14020 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.418

GnomAD3 exomes AF: 0.439 AC: 109505 AN: 249318 Hom.: 24769 AF XY: 0.445 AC XY: 60213 AN XY: 135162

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.449

Gnomad SAS exome AF: 0.468

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.442

GnomAD4 exome AF: 0.469 AC: 677266 AN: 1444636 Hom.: 160312 Cov.: 26 AF XY: 0.469 AC XY: 337687 AN XY: 719774

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.458

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.424 AC: 64433 AN: 151968 Hom.: 14018 Cov.: 32 AF XY: 0.423 AC XY: 31443 AN XY: 74286

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.420

Alfa AF: 0.453 Hom.: 2898

Bravo AF: 0.407

Asia WGS AF: 0.457 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.30

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: rs10755578; hg19: chr6-160969738; COSMIC: COSV60298976;