6-160536082-T-G

Position:

• chr6-160536082-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.5842+1773A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,028 control chromosomes in the GnomAD database, including 28,451 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 0.61 (28451 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

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]

LOC124901454 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPA	NM_005577.4	c.5842+1773A>C		intron_variant		ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.484-3435T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5842+1773A>C		intron_variant		1	NM_005577.4	ENSP00000321334	P1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92204 AN: 151910 Hom.: 28452 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.607 AC: 92232 AN: 152028 Hom.: 28451 Cov.: 32 AF XY: 0.604 AC XY: 44861 AN XY: 74292

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.577

Alfa AF: 0.646 Hom.: 42704

Bravo AF: 0.594

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.45

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: rs7449650; hg19: chr6-160957114; COSMIC: COSV60310252;