rs3124785

Variant names:

• chr6-160533473-G-A
• rs3124785
• NM_005577.4:c.5843-824C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-160533473-G-A
• chr6-160533473-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005577.4(LPA):​c.5843-824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,928 control chromosomes in the GnomAD database, including 6,228 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 0.28 (6228 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5843-824C>T		intron_variant	Intron 37 of 38	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.484-6044G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5843-824C>T		intron_variant	Intron 37 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42550 AN: 151810 Hom.: 6228 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.280 AC: 42559 AN: 151928 Hom.: 6228 Cov.: 32 AF XY: 0.279 AC XY: 20704 AN XY: 74240

African (AFR) AF: 0.297 AC: 12290 AN: 41450

American (AMR) AF: 0.201 AC: 3062 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.117 AC: 604 AN: 5154

South Asian (SAS) AF: 0.230 AC: 1107 AN: 4806

European-Finnish (FIN) AF: 0.343 AC: 3611 AN: 10538

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19987 AN: 67938

Other (OTH) AF: 0.267 AC: 563 AN: 2106

Alfa AF: 0.282 Hom.: 802

Bravo AF: 0.268

Asia WGS AF: 0.157 AC: 547 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	0.0080
DANN	Benign	0.71
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3124785; hg19: chr6-160954505; COSMIC: COSV60310245;