rs3798220

Variant names:

• chr6-160540105-T-C
• rs3798220
• NM_005577.4:c.5673A>G

Variant summary

Our verdict is Benign. The variant received -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. 12/19 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5673A>G	p.Ile1891Met	missense_variant	Exon 36 of 39	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.1072T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5673A>G	p.Ile1891Met	missense_variant	Exon 36 of 39	1	NM_005577.4	ENSP00000321334.6

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

GnomAD2 exomes AF: 0.0557 AC: 14019 AN: 251472 AF XY: 0.0455

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 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 AC: 199 AN: 33480

Gnomad4 AMR exome AF: 0.267 AC: 11930 AN: 44724

Gnomad4 ASJ exome AF: 0.00184 AC: 48 AN: 26136

Gnomad4 EAS exome AF: 0.0954 AC: 3786 AN: 39700

Gnomad4 SAS exome AF: 0.00443 AC: 382 AN: 86258

Gnomad4 FIN exome AF: 0.0109 AC: 583 AN: 53420

Gnomad4 NFE exome AF: 0.0187 AC: 20777 AN: 1112010

Gnomad4 Remaining exome AF: 0.0250 AC: 1510 AN: 60396

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 AC: 0.00861488 AN: 0.00861488

Gnomad4 AMR AF: 0.173 AC: 0.173145 AN: 0.173145

Gnomad4 ASJ AF: 0.00144 AC: 0.00144009 AN: 0.00144009

Gnomad4 EAS AF: 0.0935 AC: 0.0934959 AN: 0.0934959

Gnomad4 SAS AF: 0.00478 AC: 0.00477972 AN: 0.00477972

Gnomad4 FIN AF: 0.00933 AC: 0.00933434 AN: 0.00933434

Gnomad4 NFE AF: 0.0175 AC: 0.017469 AN: 0.017469

Gnomad4 OTH AF: 0.0440 AC: 0.0440341 AN: 0.0440341

Alfa AF: 0.0244 Hom.: 485

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

Aug 07, 2020

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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
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
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

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