rs1652507

chr6-160661429-T-C

Variant summary

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

The NM_005577.4(LPA):c.49+2737A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,106 control chromosomes in the GnomAD database, including 2,953 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 0.17 (2953 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617

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 (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.49+2737A>G		intron_variant		ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.49+2737A>G		intron_variant		1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25901 AN: 151988 Hom.: 2952 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.170 AC: 25915 AN: 152106 Hom.: 2953 Cov.: 32 AF XY: 0.178 AC XY: 13216 AN XY: 74352

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.157

Alfa AF: 0.175 Hom.: 3416

Bravo AF: 0.178

Asia WGS AF: 0.365 AC: 1265 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	4.0
Dann	Benign	0.34

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: rs1652507; hg19: chr6-161082461;