chr6-160606796-C-G

Variant names:

• chr6-160606796-C-G
• rs9457951
• NM_005577.4:c.2604-138G>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.2604-138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,347,020 control chromosomes in the GnomAD database, including 1,169 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 0.051 (686 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (483 hom.)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 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.2604-138G>C		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.2604-138G>C		intron	N/A	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7666 AN: 152078 Hom.: 680 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0430

GnomAD4 exome AF: 0.00552 AC: 6596 AN: 1194822 Hom.: 483 AF XY: 0.00479 AC XY: 2902 AN XY: 605744

African (AFR) AF: 0.177 AC: 4932 AN: 27794

American (AMR) AF: 0.00735 AC: 319 AN: 43374

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 266 AN: 24400

East Asian (EAS) AF: 0.00 AC: 0 AN: 38216

South Asian (SAS) AF: 0.000485 AC: 39 AN: 80460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48874

Middle Eastern (MID) AF: 0.0262 AC: 98 AN: 3746

European-Non Finnish (NFE) AF: 0.000359 AC: 315 AN: 876564

Other (OTH) AF: 0.0122 AC: 627 AN: 51394

GnomAD4 genome AF: 0.0506 AC: 7704 AN: 152198 Hom.: 686 Cov.: 32 AF XY: 0.0487 AC XY: 3624 AN XY: 74408

African (AFR) AF: 0.176 AC: 7299 AN: 41474

American (AMR) AF: 0.0139 AC: 212 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68022

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.0572

Asia WGS AF: 0.0120 AC: 43 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.52
PhyloP100		1.3
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: rs9457951; hg19: chr6-161027828;