rs12194138

Variant names:

• chr6-160538799-A-T
• rs12194138
• NM_005577.4:c.5736-838T>A

Variant summary

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

The NM_005577.4(LPA):​c.5736-838T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,094 control chromosomes in the GnomAD database, including 1,300 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 0.11 (1300 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5736-838T>A		intron_variant	Intron 36 of 38	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.484-718A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5736-838T>A		intron_variant	Intron 36 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16727 AN: 151976 Hom.: 1300 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0266

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.110 AC: 16717 AN: 152094 Hom.: 1300 Cov.: 32 AF XY: 0.105 AC XY: 7828 AN XY: 74336

African (AFR) AF: 0.0322 AC: 1338 AN: 41496

American (AMR) AF: 0.0797 AC: 1216 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.0352 AC: 182 AN: 5170

South Asian (SAS) AF: 0.0260 AC: 125 AN: 4808

European-Finnish (FIN) AF: 0.134 AC: 1418 AN: 10574

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11599 AN: 67988

Other (OTH) AF: 0.0992 AC: 210 AN: 2116

Alfa AF: 0.134 Hom.: 181

Bravo AF: 0.102

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.56
PhyloP100		-0.34
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: rs12194138; hg19: chr6-160959831; COSMIC: COSV60310263;