rs10455872

chr6-160589086-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005577.4(LPA):c.3947+467T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 152,252 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.042 (192 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.08

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-160589086-A-G is Benign according to our data. Variant chr6-160589086-A-G is described in ClinVar as [Benign]. Clinvar id is 225938.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.3947+467T>C		intron_variant		ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.3947+467T>C		intron_variant		1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6468 AN: 152134 Hom.: 192 Cov.: 33

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.0436

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

GnomAD4 genome AF: 0.0424 AC: 6463 AN: 152252 Hom.: 192 Cov.: 33 AF XY: 0.0392 AC XY: 2921 AN XY: 74438

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0694

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0616 Hom.: 414

Bravo AF: 0.0411

Asia WGS AF: 0.00636 AC: 23 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LIPOPROTEIN(a) POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Aug 07, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.13
Dann	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs10455872; hg19: chr6-161010118; COSMIC: COSV60310358;