rs12175867

Variant names:

• chr6-160598106-T-C
• rs12175867
• NM_005577.4:c.3287+1394A>G

Variant summary

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

The NM_005577.4(LPA):​c.3287+1394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,188 control chromosomes in the GnomAD database, including 3,539 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 0.19 (3539 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• 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]

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 = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.3287+1394A>G		intron_variant	Intron 20 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.3287+1394A>G		intron_variant	Intron 20 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28633 AN: 152070 Hom.: 3532 Cov.: 33

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.188 AC: 28651 AN: 152188 Hom.: 3539 Cov.: 33 AF XY: 0.196 AC XY: 14546 AN XY: 74386

African (AFR) AF: 0.0498 AC: 2069 AN: 41564

American (AMR) AF: 0.177 AC: 2708 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2159 AN: 5164

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4812

European-Finnish (FIN) AF: 0.301 AC: 3184 AN: 10580

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15695 AN: 67994

Other (OTH) AF: 0.214 AC: 453 AN: 2114

Alfa AF: 0.193 Hom.: 454

Bravo AF: 0.172

Asia WGS AF: 0.335 AC: 1162 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	1.2
DANN	Benign	0.67
PhyloP100		-0.41
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: rs12175867; hg19: chr6-161019138; COSMIC: COSV60299222;