rs13202636

chr6-160608696-T-Cchr6-160608696-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005577.4(LPA):c.2604-2038A>G 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 152,068 control chromosomes in the GnomAD database, including 3,761 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 (3761 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.2604-2038A>G		intron_variant		ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.2604-2038A>G		intron_variant		1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31114 AN: 151950 Hom.: 3754 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.182

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: 0.218

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

GnomAD4 genome AF: 0.205 AC: 31140 AN: 152068 Hom.: 3761 Cov.: 33 AF XY: 0.211 AC XY: 15682 AN XY: 74338

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.225

Alfa AF: 0.224 Hom.: 5622

Bravo AF: 0.191

Asia WGS AF: 0.337 AC: 1170 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.5
Dann	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs13202636; hg19: chr6-161029728; COSMIC: COSV60299420;