rs12212507

Variant names:

• chr6-160650950-G-A
• rs12212507
• NM_005577.4:c.50-453C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-160650950-G-A
• chr6-160650950-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.50-453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,196 control chromosomes in the GnomAD database, including 126 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 0.031 (126 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.50-453C>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.50-453C>T		intron_variant	Intron 1 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4772 AN: 152076 Hom.: 126 Cov.: 33

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0313 AC: 4771 AN: 152196 Hom.: 126 Cov.: 33 AF XY: 0.0290 AC XY: 2161 AN XY: 74414

African (AFR) AF: 0.00934 AC: 388 AN: 41522

American (AMR) AF: 0.0143 AC: 218 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.0310 AC: 329 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3748 AN: 67998

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.0504 Hom.: 341

Bravo AF: 0.0288

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.63
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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: rs12212507; hg19: chr6-161071982;