6-160577116-G-T

Variant names:

• chr6-160577116-G-T
• rs3798221
• NM_005577.4:c.4631+20C>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.4631+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,610,376 control chromosomes in the GnomAD database, including 35,680 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 (3161 hom., cov: 31)
  • Exomes 𝑓: 0.20 (32519 hom.)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 39 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	NM_005577.4	MANE Select	c.4631+20C>A		intron	N/A	NP_005568.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	ENST00000316300.10	TSL:1 MANE Select	c.4631+20C>A		intron	N/A	ENSP00000321334.6
	LPA	ENST00000870146.1		c.4628+20C>A		intron	N/A	ENSP00000540205.1
	LPA	ENST00000870147.1		c.4313+20C>A		intron	N/A	ENSP00000540206.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29293 AN: 151890 Hom.: 3153 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.213 AC: 53357 AN: 250000 AF XY: 0.220

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.395

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.203 AC: 296775 AN: 1458368 Hom.: 32519 Cov.: 32 AF XY: 0.206 AC XY: 149705 AN XY: 725598

African (AFR) AF: 0.144 AC: 4809 AN: 33384

American (AMR) AF: 0.135 AC: 6024 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4886 AN: 26104

East Asian (EAS) AF: 0.428 AC: 16970 AN: 39634

South Asian (SAS) AF: 0.273 AC: 23537 AN: 86128

European-Finnish (FIN) AF: 0.242 AC: 12913 AN: 53346

Middle Eastern (MID) AF: 0.281 AC: 1404 AN: 5002

European-Non Finnish (NFE) AF: 0.192 AC: 213469 AN: 1109868

Other (OTH) AF: 0.212 AC: 12763 AN: 60200

GnomAD4 genome AF: 0.193 AC: 29318 AN: 152008 Hom.: 3161 Cov.: 31 AF XY: 0.198 AC XY: 14667 AN XY: 74260

African (AFR) AF: 0.142 AC: 5906 AN: 41486

American (AMR) AF: 0.175 AC: 2666 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2043 AN: 5136

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4812

European-Finnish (FIN) AF: 0.244 AC: 2572 AN: 10558

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

European-Non Finnish (NFE) AF: 0.196 AC: 13348 AN: 67966

Other (OTH) AF: 0.217 AC: 457 AN: 2110

Alfa AF: 0.193 Hom.: 3102

Bravo AF: 0.185

Asia WGS AF: 0.328 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.35
PhyloP100		-1.1
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: rs3798221; hg19: chr6-160998148; COSMIC: COSV60299200;