6-160539327-T-C

Variant names:

• chr6-160539327-T-C
• rs6919346
• NM_005577.4:c.5735+716A>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.5735+716A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,250 control chromosomes in the GnomAD database, including 59,753 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 0.88 (59753 hom., cov: 32)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 40 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5735+716A>G		intron_variant	Intron 36 of 38	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1	n.484-190T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5735+716A>G		intron_variant	Intron 36 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134373 AN: 152132 Hom.: 59694 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.883 AC: 134492 AN: 152250 Hom.: 59753 Cov.: 32 AF XY: 0.888 AC XY: 66074 AN XY: 74438

African (AFR) AF: 0.968 AC: 40237 AN: 41558

American (AMR) AF: 0.889 AC: 13595 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2652 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5182 AN: 5186

South Asian (SAS) AF: 0.959 AC: 4630 AN: 4828

European-Finnish (FIN) AF: 0.863 AC: 9121 AN: 10572

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56174 AN: 68016

Other (OTH) AF: 0.876 AC: 1851 AN: 2114

Alfa AF: 0.844 Hom.: 199168

Bravo AF: 0.886

Asia WGS AF: 0.977 AC: 3398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.2
DANN	Benign	0.42
PhyloP100		0.20
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: rs6919346; hg19: chr6-160960359; COSMIC: COSV60310271;