rs7761293

Variant names:

• chr6-160549931-G-A
• rs7761293
• NM_005577.4:c.4974-1272C>T

Variant summary

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

The NM_005577.4(LPA):​c.4974-1272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,134 control chromosomes in the GnomAD database, including 23,104 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 0.53 (23104 hom., cov: 34)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 16 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.4974-1272C>T		intron_variant	Intron 30 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.4974-1272C>T		intron_variant	Intron 30 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79853 AN: 152016 Hom.: 23065 Cov.: 34

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.525 AC: 79929 AN: 152134 Hom.: 23104 Cov.: 34 AF XY: 0.517 AC XY: 38441 AN XY: 74374

African (AFR) AF: 0.762 AC: 31634 AN: 41526

American (AMR) AF: 0.414 AC: 6324 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1622 AN: 3468

East Asian (EAS) AF: 0.121 AC: 629 AN: 5182

South Asian (SAS) AF: 0.292 AC: 1410 AN: 4826

European-Finnish (FIN) AF: 0.463 AC: 4903 AN: 10592

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31895 AN: 67944

Other (OTH) AF: 0.475 AC: 1003 AN: 2112

Alfa AF: 0.476 Hom.: 35951

Bravo AF: 0.531

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.75
PhyloP100		-1.2
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: rs7761293; hg19: chr6-160970963; COSMIC: COSV60310316;