rs7755463

Positions:

• chr6-160591238-C-T

Variant summary

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

The ENST00000316300.10(LPA):​c.3630-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,105,236 control chromosomes in the GnomAD database, including 4,015 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 0.10 (2537 hom., cov: 33)
  • Exomes 𝑓: 0.012 (1478 hom.)
• Consequence: LPA ENST00000316300.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPA	NM_005577.4	c.3630-137G>A		intron_variant		ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.3630-137G>A		intron_variant		1	NM_005577.4	ENSP00000321334	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15469 AN: 152096 Hom.: 2518 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.0865

GnomAD4 exome AF: 0.0119 AC: 11327 AN: 953024 Hom.: 1478 AF XY: 0.0103 AC XY: 4999 AN XY: 484894

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000973

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00118

Gnomad4 OTH exome AF: 0.0293

GnomAD4 genome AF: 0.102 AC: 15528 AN: 152212 Hom.: 2537 Cov.: 33 AF XY: 0.0984 AC XY: 7322 AN XY: 74434

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0519 Hom.: 251

Bravo AF: 0.116

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.53

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: rs7755463; hg19: chr6-161012270;