chr6-160648909-G-A

Variant names:

• chr6-160648909-G-A
• rs10945682
• NM_005577.4:c.209+1429C>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.209+1429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,788 control chromosomes in the GnomAD database, including 14,288 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 0.42 (14288 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 18 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.209+1429C>T		intron_variant	Intron 2 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.209+1429C>T		intron_variant	Intron 2 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64175 AN: 151668 Hom.: 14255 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.423 AC: 64268 AN: 151788 Hom.: 14288 Cov.: 32 AF XY: 0.422 AC XY: 31293 AN XY: 74150

African (AFR) AF: 0.569 AC: 23533 AN: 41374

American (AMR) AF: 0.328 AC: 5006 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1153 AN: 3466

East Asian (EAS) AF: 0.422 AC: 2181 AN: 5166

South Asian (SAS) AF: 0.370 AC: 1782 AN: 4810

European-Finnish (FIN) AF: 0.393 AC: 4138 AN: 10536

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25042 AN: 67884

Other (OTH) AF: 0.402 AC: 847 AN: 2108

Alfa AF: 0.382 Hom.: 21619

Bravo AF: 0.422

Asia WGS AF: 0.417 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.23
DANN	Benign	0.24
PhyloP100		-0.036
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: rs10945682; hg19: chr6-161069941;