chr6-160578008-G-A

Variant names:

• chr6-160578008-G-A
• rs9364564
• NM_005577.4:c.4471+515C>T

Variant summary

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

The NM_005577.4(LPA):​c.4471+515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,076 control chromosomes in the GnomAD database, including 2,874 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 0.18 (2874 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 5 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=-0.96).
• 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 rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.4471+515C>T		intron_variant	Intron 27 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.4471+515C>T		intron_variant	Intron 27 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27028 AN: 151958 Hom.: 2866 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.178 AC: 27049 AN: 152076 Hom.: 2874 Cov.: 32 AF XY: 0.184 AC XY: 13643 AN XY: 74324

African (AFR) AF: 0.0896 AC: 3719 AN: 41506

American (AMR) AF: 0.170 AC: 2595 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2043 AN: 5142

South Asian (SAS) AF: 0.266 AC: 1276 AN: 4804

European-Finnish (FIN) AF: 0.243 AC: 2574 AN: 10578

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13362 AN: 67986

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.192 Hom.: 1411

Bravo AF: 0.168

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.80
DANN	Benign	0.43
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9364564; hg19: chr6-160999040; COSMIC: COSV60299206;