6-160663610-C-T

Position:

• chr6-160663610-C-T

Variant summary

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

The NM_005577.4(LPA):​c.49+556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,032 control chromosomes in the GnomAD database, including 18,046 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 0.48 (18046 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPA	NM_005577.4	c.49+556G>A		intron_variant		ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.49+556G>A		intron_variant		1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72863 AN: 151914 Hom.: 18037 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.479 AC: 72893 AN: 152032 Hom.: 18046 Cov.: 33 AF XY: 0.476 AC XY: 35398 AN XY: 74322

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.528

Alfa AF: 0.543 Hom.: 41387

Bravo AF: 0.465

Asia WGS AF: 0.370 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.64

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: rs9346833; hg19: chr6-161084642;