6-160601391-T-C

Variant names:

• chr6-160601391-T-C
• rs13192132
• NM_005577.4:c.2946-293A>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.2946-293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,100 control chromosomes in the GnomAD database, including 7,719 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 0.30 (7719 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.2946-293A>G		intron_variant	Intron 18 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.2946-293A>G		intron_variant	Intron 18 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45727 AN: 151982 Hom.: 7708 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.301 AC: 45758 AN: 152100 Hom.: 7719 Cov.: 32 AF XY: 0.304 AC XY: 22618 AN XY: 74332

African (AFR) AF: 0.148 AC: 6154 AN: 41524

American (AMR) AF: 0.284 AC: 4335 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2180 AN: 5158

South Asian (SAS) AF: 0.368 AC: 1767 AN: 4802

European-Finnish (FIN) AF: 0.392 AC: 4143 AN: 10576

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24892 AN: 67964

Other (OTH) AF: 0.304 AC: 642 AN: 2114

Alfa AF: 0.264 Hom.: 1185

Bravo AF: 0.284

Asia WGS AF: 0.387 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs13192132; hg19: chr6-161022423;