chr6-160664263-A-G

Position:

• chr6-160664263-A-G

Variant summary

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

The ENST00000316300.10(LPA):​c.-49T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,575,796 control chromosomes in the GnomAD database, including 582,072 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 0.89 (59980 hom., cov: 32)
  • Exomes 𝑓: 0.86 (522092 hom.)
• Consequence: LPA ENST00000316300.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPA	NM_005577.4	c.-49T>C		5_prime_UTR_variant	1/39	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.-49T>C		5_prime_UTR_variant	1/39	1	NM_005577.4	ENSP00000321334	P1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134688 AN: 152112 Hom.: 59928 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.877

GnomAD3 exomes AF: 0.764 AC: 112222 AN: 146928 Hom.: 51166 AF XY: 0.753 AC XY: 60230 AN XY: 79980

Gnomad AFR exome AF: 0.937

Gnomad AMR exome AF: 0.855

Gnomad ASJ exome AF: 0.802

Gnomad EAS exome AF: 0.675

Gnomad SAS exome AF: 0.678

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.753

Gnomad OTH exome AF: 0.785

GnomAD4 exome AF: 0.855 AC: 1217433 AN: 1423566 Hom.: 522092 Cov.: 29 AF XY: 0.852 AC XY: 604580 AN XY: 709458

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.926

Gnomad4 ASJ exome AF: 0.869

Gnomad4 EAS exome AF: 0.786

Gnomad4 SAS exome AF: 0.773

Gnomad4 FIN exome AF: 0.853

Gnomad4 NFE exome AF: 0.858

Gnomad4 OTH exome AF: 0.855

GnomAD4 genome AF: 0.885 AC: 134795 AN: 152230 Hom.: 59980 Cov.: 32 AF XY: 0.882 AC XY: 65604 AN XY: 74418

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.879

Alfa AF: 0.865 Hom.: 10534

Bravo AF: 0.895

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
DANN	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1853021; hg19: chr6-161085295;