rs7450411

chr6-160589322-C-Achr6-160589322-C-Gchr6-160589322-C-T

Variant summary

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

The NM_005577.4(LPA):c.3947+231G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,130 control chromosomes in the GnomAD database, including 3,172 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 (3172 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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 = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.3947+231G>T		intron_variant		ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.3947+231G>T		intron_variant		1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29345 AN: 152012 Hom.: 3164 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.193 AC: 29370 AN: 152130 Hom.: 3172 Cov.: 33 AF XY: 0.198 AC XY: 14696 AN XY: 74348

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.216

Alfa AF: 0.0935 Hom.: 139

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	-0.90
Cadd	Benign	1.3
Dann	Benign	0.39

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: rs7450411; hg19: chr6-161010354; COSMIC: COSV60299216;