6-160598834-A-G

Variant names:

• chr6-160598834-A-G
• rs6926458
• NM_005577.4:c.3287+666T>C

Variant summary

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

The NM_005577.4(LPA):​c.3287+666T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,196 control chromosomes in the GnomAD database, including 3,740 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 0.20 (3740 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 17 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005577.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	NM_005577.4	MANE Select	c.3287+666T>C		intron	N/A	NP_005568.2	P08519

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	ENST00000316300.10	TSL:1 MANE Select	c.3287+666T>C		intron	N/A	ENSP00000321334.6	P08519
	LPA	ENST00000870146.1		c.3284+666T>C		intron	N/A	ENSP00000540205.1
	LPA	ENST00000870147.1		c.3287+666T>C		intron	N/A	ENSP00000540206.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31125 AN: 152078 Hom.: 3734 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.205 AC: 31149 AN: 152196 Hom.: 3740 Cov.: 32 AF XY: 0.211 AC XY: 15675 AN XY: 74400

African (AFR) AF: 0.107 AC: 4435 AN: 41536

American (AMR) AF: 0.183 AC: 2799 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2159 AN: 5168

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3190 AN: 10598

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15708 AN: 68004

Other (OTH) AF: 0.224 AC: 473 AN: 2114

Alfa AF: 0.219 Hom.: 13943

Bravo AF: 0.191

Asia WGS AF: 0.338 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-0.30
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: rs6926458; hg19: chr6-161019866; COSMIC: COSV60299364;