rs200086599

Variant names:

• chr6-160541153-A-G
• rs200086599
• NM_005577.4:c.5548T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005577.4(LPA):​c.5548T>C​(p.Leu1850Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,070 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (8 hom.)
• Consequence: LPA NM_005577.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-160541153-A-G is Benign according to our data. Variant chr6-160541153-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657111.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.46 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5548T>C	p.Leu1850Leu	synonymous_variant	Exon 35 of 39	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5548T>C	p.Leu1850Leu	synonymous_variant	Exon 35 of 39	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 308 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00345

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00235 AC: 591 AN: 251324 AF XY: 0.00241

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00370

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00291 AC: 4248 AN: 1461742 Hom.: 8 Cov.: 30 AF XY: 0.00285 AC XY: 2076 AN XY: 727180

African (AFR) AF: 0.000329 AC: 11 AN: 33474

American (AMR) AF: 0.00112 AC: 50 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00191 AC: 165 AN: 86256

European-Finnish (FIN) AF: 0.00307 AC: 164 AN: 53414

Middle Eastern (MID) AF: 0.00728 AC: 42 AN: 5768

European-Non Finnish (NFE) AF: 0.00325 AC: 3613 AN: 1111888

Other (OTH) AF: 0.00275 AC: 166 AN: 60388

GnomAD4 genome AF: 0.00202 AC: 308 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74486

African (AFR) AF: 0.000433 AC: 18 AN: 41592

American (AMR) AF: 0.000458 AC: 7 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00345 AC: 235 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00264 Hom.: 0

Bravo AF: 0.00180

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00376

EpiControl AF: 0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LPA: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200086599; hg19: chr6-160962185;