6-160548064-C-T

Variant names:

• chr6-160548064-C-T
• rs4708871
• NM_005577.4:c.5156-127G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005577.4(LPA):​c.5156-127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 880,706 control chromosomes in the GnomAD database, including 418,605 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 0.98 (73034 hom., cov: 32)
  • Exomes 𝑓: 0.97 (345571 hom.)
• Consequence: LPA NM_005577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4	c.5156-127G>A		intron_variant	Intron 31 of 38	ENST00000316300.10	NP_005568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10	c.5156-127G>A		intron_variant	Intron 31 of 38	1	NM_005577.4	ENSP00000321334.6

Frequencies

GnomAD3 genomes AF: 0.979 AC: 149026 AN: 152192 Hom.: 72972 Cov.: 32

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.974

GnomAD4 exome AF: 0.974 AC: 709443 AN: 728396 Hom.: 345571 AF XY: 0.975 AC XY: 376053 AN XY: 385844

Gnomad4 AFR exome AF: 0.994

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 0.955

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.980

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.974

GnomAD4 genome AF: 0.979 AC: 149147 AN: 152310 Hom.: 73034 Cov.: 32 AF XY: 0.980 AC XY: 72985 AN XY: 74474

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.974

Alfa AF: 0.973 Hom.: 17082

Bravo AF: 0.979

Asia WGS AF: 0.995 AC: 3461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4708871; hg19: chr6-160969096;