NM_005577.4:c.49+2503A>G

Variant names:

• chr6-160661663-T-C
• rs1367211
• NM_005577.4:c.49+2503A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005577.4(LPA):​c.49+2503A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,030 control chromosomes in the GnomAD database, including 34,474 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34474 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 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.49+2503A>G		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.49+2503A>G		intron	N/A	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101186 AN: 151912 Hom.: 34462 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.666 AC: 101229 AN: 152030 Hom.: 34474 Cov.: 32 AF XY: 0.670 AC XY: 49764 AN XY: 74318

African (AFR) AF: 0.509 AC: 21081 AN: 41424

American (AMR) AF: 0.747 AC: 11420 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3470

East Asian (EAS) AF: 0.813 AC: 4204 AN: 5170

South Asian (SAS) AF: 0.690 AC: 3325 AN: 4818

European-Finnish (FIN) AF: 0.757 AC: 7993 AN: 10552

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.716 AC: 48693 AN: 68000

Other (OTH) AF: 0.694 AC: 1465 AN: 2110

Alfa AF: 0.703 Hom.: 161395

Bravo AF: 0.661

Asia WGS AF: 0.741 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.81
PhyloP100		-0.12
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: rs1367211; hg19: chr6-161082695;