6-160663124-A-G

Variant names:

• chr6-160663124-A-G
• rs1321195
• NM_005577.4:c.49+1042T>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.49+1042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,290 control chromosomes in the GnomAD database, including 60,031 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 0.89 (60031 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 8 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.49+1042T>C		intron_variant	Intron 1 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.49+1042T>C		intron_variant	Intron 1 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134767 AN: 152172 Hom.: 59973 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.886 AC: 134881 AN: 152290 Hom.: 60031 Cov.: 33 AF XY: 0.882 AC XY: 65651 AN XY: 74458

African (AFR) AF: 0.968 AC: 40246 AN: 41570

American (AMR) AF: 0.898 AC: 13749 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2979 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4167 AN: 5170

South Asian (SAS) AF: 0.778 AC: 3753 AN: 4824

European-Finnish (FIN) AF: 0.848 AC: 9000 AN: 10608

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58299 AN: 68020

Other (OTH) AF: 0.879 AC: 1861 AN: 2116

Alfa AF: 0.890 Hom.: 8272

Bravo AF: 0.895

Asia WGS AF: 0.820 AC: 2853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.7
DANN	Benign	0.24
PhyloP100		-0.88
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: rs1321195; hg19: chr6-161084156;