rs1367209

Variant names:

• chr6-160661815-G-A
• rs1367209
• NM_005577.4:c.49+2351C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-160661815-G-A
• chr6-160661815-G-T

Variant summary

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

The NM_005577.4(LPA):​c.49+2351C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,080 control chromosomes in the GnomAD database, including 34,438 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 0.67 (34438 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.49+2351C>T		intron_variant	Intron 1 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.49+2351C>T		intron_variant	Intron 1 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101151 AN: 151962 Hom.: 34426 Cov.: 33

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.665 AC: 101194 AN: 152080 Hom.: 34438 Cov.: 33 AF XY: 0.669 AC XY: 49756 AN XY: 74360

African (AFR) AF: 0.508 AC: 21051 AN: 41438

American (AMR) AF: 0.747 AC: 11425 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4170 AN: 5174

South Asian (SAS) AF: 0.689 AC: 3325 AN: 4826

European-Finnish (FIN) AF: 0.758 AC: 8027 AN: 10592

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48682 AN: 67980

Other (OTH) AF: 0.695 AC: 1467 AN: 2112

Alfa AF: 0.697 Hom.: 5355

Bravo AF: 0.660

Asia WGS AF: 0.737 AC: 2566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.47
PhyloP100		1.1
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: rs1367209; hg19: chr6-161082847;