rs3798220

chr6-160540105-T-C

Variant summary

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

The NM_005577.4(LPA):c.5673A>G(p.Ile1891Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,614,110 control chromosomes in the GnomAD database, including 2,565 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.032 (306 hom., cov: 32)
  • Exomes 𝑓: 0.027 (2259 hom.)
• Consequence: LPA NM_005577.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.210

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004463792).
• BP6: Variant 6-160540105-T-C is Benign according to our data. Variant chr6-160540105-T-C is described in ClinVar as [Benign]. Clinvar id is 975030.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4	c.5673A>G	p.Ile1891Met	missense_variant	36/39	ENST00000316300.10
LOC124901454	XR_007059844.1	n.1072T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10	c.5673A>G	p.Ile1891Met	missense_variant	36/39	1	NM_005577.4	P1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4885 AN: 152100 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.00478

Gnomad FIN AF: 0.00933

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0445

GnomAD3 exomes AF: 0.0557 AC: 14019 AN: 251472 Hom.: 1639 AF XY: 0.0455 AC XY: 6190 AN XY: 135910

Gnomad AFR exome AF: 0.00787

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.0896

Gnomad SAS exome AF: 0.00392

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.0174

Gnomad OTH exome AF: 0.0443

GnomAD4 exome AF: 0.0268 AC: 39248 AN: 1461892 Hom.: 2259 Cov.: 32 AF XY: 0.0252 AC XY: 18337 AN XY: 727246

Gnomad4 AFR exome AF: 0.00594

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.0954

Gnomad4 SAS exome AF: 0.00443

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0250

GnomAD4 genome AF: 0.0322 AC: 4908 AN: 152218 Hom.: 306 Cov.: 32 AF XY: 0.0336 AC XY: 2499 AN XY: 74416

Gnomad4 AFR AF: 0.00861

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0935

Gnomad4 SAS AF: 0.00478

Gnomad4 FIN AF: 0.00933

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0205 Hom.: 90

Bravo AF: 0.0470

TwinsUK AF: 0.0167 AC: 62

ALSPAC AF: 0.0239 AC: 92

ESP6500AA AF: 0.00862 AC: 38

ESP6500EA AF: 0.0195 AC: 168

ExAC AF: 0.0448 AC: 5444

Asia WGS AF: 0.0340 AC: 119 AN: 3478

EpiCase AF: 0.0168

EpiControl AF: 0.0172

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_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	12
Dann	Benign	0.97
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.053	N
MetaRNN	Benign	0.0045	T
MetaSVM	Uncertain	-0.052	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.32
Sift	Benign	0.12	T
Sift4G	Uncertain	0.022	D
Vest4		0.10
ClinPred		0.017	T
GERP RS		3.0
gMVP		0.26

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: rs3798220; hg19: chr6-160961137; COSMIC: COSV60302696;