NM_005577.4:c.3947+467T>C

Variant names:

• chr6-160589086-A-G
• rs10455872
• NM_005577.4:c.3947+467T>C

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.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
• Publications: 423 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005577.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	NM_005577.4	MANE Select	c.3947+467T>C		intron	N/A	NP_005568.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	ENST00000316300.10	TSL:1 MANE Select	c.3947+467T>C		intron	N/A	ENSP00000321334.6
	LPA	ENST00000870146.1		c.3944+467T>C		intron	N/A	ENSP00000540205.1
	LPA	ENST00000870147.1		c.3630-2456T>C		intron	N/A	ENSP00000540206.1

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

African (AFR) AF: 0.0121 AC: 505 AN: 41572

American (AMR) AF: 0.0384 AC: 586 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3472

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5156

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4832

European-Finnish (FIN) AF: 0.0354 AC: 376 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0694 AC: 4723 AN: 68006

Other (OTH) AF: 0.0431 AC: 91 AN: 2110

Alfa AF: 0.0596 Hom.: 997

Bravo AF: 0.0411

Asia WGS AF: 0.00636 AC: 23 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	LIPOPROTEIN(a) POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.37
PhyloP100		-2.1
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: rs10455872; hg19: chr6-161010118; COSMIC: COSV60310358;