6-160597142-C-T

Variant names:

• chr6-160597142-C-T
• rs7770628
• NM_005577.4:c.3288-1607G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005577.4(LPA):​c.3288-1607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,014 control chromosomes in the GnomAD database, including 31,059 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 0.63 (31059 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 45 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.3288-1607G>A		intron_variant	Intron 20 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.3288-1607G>A		intron_variant	Intron 20 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95679 AN: 151896 Hom.: 31000 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.630 AC: 95800 AN: 152014 Hom.: 31059 Cov.: 32 AF XY: 0.635 AC XY: 47184 AN XY: 74294

African (AFR) AF: 0.757 AC: 31385 AN: 41466

American (AMR) AF: 0.675 AC: 10309 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3470

East Asian (EAS) AF: 0.884 AC: 4573 AN: 5172

South Asian (SAS) AF: 0.684 AC: 3300 AN: 4822

European-Finnish (FIN) AF: 0.570 AC: 6024 AN: 10566

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36503 AN: 67930

Other (OTH) AF: 0.603 AC: 1272 AN: 2110

Alfa AF: 0.569 Hom.: 106261

Bravo AF: 0.642

Asia WGS AF: 0.786 AC: 2729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.82
DANN	Benign	0.25
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7770628; hg19: chr6-161018174;