chr6-160660810-C-T

Variant names:

• chr6-160660810-C-T
• rs1321196
• NM_005577.4:c.49+3356G>A

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+3356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,896 control chromosomes in the GnomAD database, including 28,700 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 (28700 hom., cov: 31)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732
• Publications: 12 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.49+3356G>A		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+3356G>A		intron_variant	Intron 1 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93126 AN: 151780 Hom.: 28698 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.613 AC: 93151 AN: 151896 Hom.: 28700 Cov.: 31 AF XY: 0.613 AC XY: 45497 AN XY: 74230

African (AFR) AF: 0.559 AC: 23140 AN: 41416

American (AMR) AF: 0.683 AC: 10437 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2977 AN: 5158

South Asian (SAS) AF: 0.630 AC: 3035 AN: 4818

European-Finnish (FIN) AF: 0.607 AC: 6386 AN: 10512

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42922 AN: 67942

Other (OTH) AF: 0.622 AC: 1307 AN: 2102

Alfa AF: 0.633 Hom.: 50068

Bravo AF: 0.618

Asia WGS AF: 0.586 AC: 2038 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.44
PhyloP100		0.73
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: rs1321196; hg19: chr6-161081842;