6-160577116-G-T

Position:

• chr6-160577116-G-T

Variant summary

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

The NM_005577.4(LPA):​c.4631+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,610,376 control chromosomes in the GnomAD database, including 35,680 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 0.19 (3161 hom., cov: 31)
  • Exomes 𝑓: 0.20 (32519 hom.)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPA	NM_005577.4	c.4631+20C>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.4631+20C>A		intron_variant		1	NM_005577.4	ENSP00000321334	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29293 AN: 151890 Hom.: 3153 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.213 AC: 53357 AN: 250000 Hom.: 6381 AF XY: 0.220 AC XY: 29813 AN XY: 135582

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.395

Gnomad SAS exome AF: 0.275

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.203 AC: 296775 AN: 1458368 Hom.: 32519 Cov.: 32 AF XY: 0.206 AC XY: 149705 AN XY: 725598

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.193 AC: 29318 AN: 152008 Hom.: 3161 Cov.: 31 AF XY: 0.198 AC XY: 14667 AN XY: 74260

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.217

Alfa AF: 0.194 Hom.: 2337

Bravo AF: 0.185

Asia WGS AF: 0.328 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.35

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: rs3798221; hg19: chr6-160998148; COSMIC: COSV60299200;