6-160587613-C-T

Variant names:

• chr6-160587613-C-T
• rs4073498
• NM_005577.4:c.3948-983G>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.3948-983G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,898 control chromosomes in the GnomAD database, including 13,223 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 0.41 (13223 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 6 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.3948-983G>A		intron_variant	Intron 24 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.3948-983G>A		intron_variant	Intron 24 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61494 AN: 151780 Hom.: 13193 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.405 AC: 61586 AN: 151898 Hom.: 13223 Cov.: 32 AF XY: 0.405 AC XY: 30051 AN XY: 74202

African (AFR) AF: 0.559 AC: 23154 AN: 41448

American (AMR) AF: 0.320 AC: 4875 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2056 AN: 5144

South Asian (SAS) AF: 0.359 AC: 1722 AN: 4802

European-Finnish (FIN) AF: 0.371 AC: 3907 AN: 10532

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23402 AN: 67956

Other (OTH) AF: 0.392 AC: 826 AN: 2108

Alfa AF: 0.225 Hom.: 514

Bravo AF: 0.405

Asia WGS AF: 0.405 AC: 1405 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	1.3
DANN	Benign	0.75
PhyloP100		-0.22
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: rs4073498; hg19: chr6-161008645;