6-160542198-T-C

Variant names:

• chr6-160542198-T-C
• rs11751605
• NM_005577.4:c.5519+490A>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.5519+490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,266 control chromosomes in the GnomAD database, including 969 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 0.090 (969 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 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.5519+490A>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.5519+490A>G		intron	N/A	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13753 AN: 152148 Hom.: 969 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.0783

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

GnomAD4 genome AF: 0.0903 AC: 13745 AN: 152266 Hom.: 969 Cov.: 32 AF XY: 0.0843 AC XY: 6278 AN XY: 74442

African (AFR) AF: 0.0265 AC: 1103 AN: 41560

American (AMR) AF: 0.0670 AC: 1025 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4830

European-Finnish (FIN) AF: 0.0871 AC: 923 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10228 AN: 68020

Other (OTH) AF: 0.0770 AC: 163 AN: 2116

Alfa AF: 0.125 Hom.: 2685

Bravo AF: 0.0854

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		0.014
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: rs11751605; hg19: chr6-160963230; COSMIC: COSV60310278;