rs7450411

Variant names:

• chr6-160589322-C-A
• rs7450411
• NM_005577.4:c.3947+231G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-160589322-C-A
• chr6-160589322-C-G
• chr6-160589322-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005577.4(LPA):​c.3947+231G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,130 control chromosomes in the GnomAD database, including 3,172 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 0.19 (3172 hom., cov: 33)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.3947+231G>T		intron_variant	Intron 24 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.3947+231G>T		intron_variant	Intron 24 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29345 AN: 152012 Hom.: 3164 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.193 AC: 29370 AN: 152130 Hom.: 3172 Cov.: 33 AF XY: 0.198 AC XY: 14696 AN XY: 74348

African (AFR) AF: 0.143 AC: 5917 AN: 41518

American (AMR) AF: 0.175 AC: 2671 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2065 AN: 5170

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4820

European-Finnish (FIN) AF: 0.243 AC: 2574 AN: 10574

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13358 AN: 67982

Other (OTH) AF: 0.216 AC: 457 AN: 2112

Alfa AF: 0.0935 Hom.: 139

Bravo AF: 0.185

Asia WGS AF: 0.328 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.32
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: rs7450411; hg19: chr6-161010354; COSMIC: COSV60299216;