chr6-160549931-G-A

Position:

• chr6-160549931-G-A

Variant summary

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

The NM_005577.4(LPA):​c.4974-1272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,134 control chromosomes in the GnomAD database, including 23,104 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 0.53 (23104 hom., cov: 34)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.4974-1272C>T		intron_variant		ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.4974-1272C>T		intron_variant		1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79853 AN: 152016 Hom.: 23065 Cov.: 34

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.525 AC: 79929 AN: 152134 Hom.: 23104 Cov.: 34 AF XY: 0.517 AC XY: 38441 AN XY: 74374

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.475

Alfa AF: 0.469 Hom.: 25051

Bravo AF: 0.531

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.75

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: rs7761293; hg19: chr6-160970963; COSMIC: COSV60310316;