rs186413938

Variant names:

• chr6-160531748-C-T
• rs186413938
• NM_005577.4:c.6104G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005577.4(LPA):​c.6104G>A​(p.Gly2035Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,058 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (1 hom.)
• Consequence: LPA NM_005577.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93
• Publications: 4 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]

LOC124901454 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052057803).
• BP6: Variant 6-160531748-C-T is Benign according to our data. Variant chr6-160531748-C-T is described in ClinVar as [Benign]. Clinvar id is 1879678.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.6104G>A	p.Gly2035Glu	missense_variant	Exon 39 of 39	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.484-7769C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.6104G>A	p.Gly2035Glu	missense_variant	Exon 39 of 39	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000915 AC: 230 AN: 251434 AF XY: 0.000964

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00205 AC: 3001 AN: 1461796 Hom.: 1 Cov.: 30 AF XY: 0.00201 AC XY: 1461 AN XY: 727210

African (AFR) AF: 0.000269 AC: 9 AN: 33470

American (AMR) AF: 0.000582 AC: 26 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00257 AC: 2860 AN: 1111958

Other (OTH) AF: 0.00167 AC: 101 AN: 60394

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152262 Hom.: 1 Cov.: 32 AF XY: 0.000913 AC XY: 68 AN XY: 74442

African (AFR) AF: 0.000554 AC: 23 AN: 41544

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00225 AC: 153 AN: 68020

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00181 Hom.: 1

Bravo AF: 0.00124

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.000898 AC: 109

EpiCase AF: 0.00202

EpiControl AF: 0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LPA: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.0060
DANN	Benign	0.81
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0051	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.99	T
PhyloP100		-1.9
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.16
Sift	Benign	0.63	T
Sift4G	Benign	0.20	T
Vest4		0.062
MVP		0.030
ClinPred		0.0077	T
GERP RS		-1.0
gMVP		0.37
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs186413938; hg19: chr6-160952780; COSMIC: COSV100307115;