6-160536082-T-G

Variant names:

• chr6-160536082-T-G
• rs7449650
• NM_005577.4:c.5842+1773A>C

Variant summary

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

The NM_005577.4(LPA):​c.5842+1773A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,028 control chromosomes in the GnomAD database, including 28,451 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 0.61 (28451 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5842+1773A>C		intron_variant	Intron 37 of 38	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.484-3435T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5842+1773A>C		intron_variant	Intron 37 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92204 AN: 151910 Hom.: 28452 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.607 AC: 92232 AN: 152028 Hom.: 28451 Cov.: 32 AF XY: 0.604 AC XY: 44861 AN XY: 74292

African (AFR) AF: 0.540 AC: 22377 AN: 41460

American (AMR) AF: 0.567 AC: 8659 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2178 AN: 3470

East Asian (EAS) AF: 0.455 AC: 2344 AN: 5148

South Asian (SAS) AF: 0.553 AC: 2657 AN: 4808

European-Finnish (FIN) AF: 0.648 AC: 6848 AN: 10574

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45193 AN: 67972

Other (OTH) AF: 0.577 AC: 1219 AN: 2112

Alfa AF: 0.643 Hom.: 59727

Bravo AF: 0.594

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.45
PhyloP100		-0.78
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: rs7449650; hg19: chr6-160957114; COSMIC: COSV60310252;