rs41264848

Variant names:

• chr6-160547936-G-A
• rs41264848
• NM_005577.4:c.5157C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-160547936-G-A
• chr6-160547936-G-C
• chr6-160547936-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005577.4(LPA):​c.5157C>T​(p.Asp1719Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,613,738 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (95 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (110 hom.)
• Consequence: LPA NM_005577.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00009096
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.287
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 6-160547936-G-A is Benign according to our data. Variant chr6-160547936-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 979150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.287 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	NM_005577.4	MANE Select	c.5157C>T	p.Asp1719Asp	splice_region synonymous	Exon 32 of 39	NP_005568.2	P08519

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	ENST00000316300.10	TSL:1 MANE Select	c.5157C>T	p.Asp1719Asp	splice_region synonymous	Exon 32 of 39	ENSP00000321334.6	P08519
	LPA	ENST00000870146.1		c.5154C>T	p.Asp1718Asp	splice_region synonymous	Exon 32 of 39	ENSP00000540205.1
	LPA	ENST00000870147.1		c.4839C>T	p.Asp1613Asp	splice_region synonymous	Exon 30 of 37	ENSP00000540206.1

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3191 AN: 151786 Hom.: 93 Cov.: 31

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.0226

GnomAD2 exomes AF: 0.00866 AC: 2167 AN: 250290 AF XY: 0.00761

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.0279

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00353

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.00470 AC: 6874 AN: 1461834 Hom.: 110 Cov.: 32 AF XY: 0.00450 AC XY: 3272 AN XY: 727224

African (AFR) AF: 0.0629 AC: 2107 AN: 33476

American (AMR) AF: 0.0135 AC: 602 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 785 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53414

Middle Eastern (MID) AF: 0.0239 AC: 138 AN: 5766

European-Non Finnish (NFE) AF: 0.00226 AC: 2518 AN: 1111972

Other (OTH) AF: 0.0115 AC: 694 AN: 60390

GnomAD4 genome AF: 0.0211 AC: 3207 AN: 151904 Hom.: 95 Cov.: 31 AF XY: 0.0203 AC XY: 1507 AN XY: 74244

African (AFR) AF: 0.0634 AC: 2625 AN: 41378

American (AMR) AF: 0.0134 AC: 205 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4802

European-Finnish (FIN) AF: 0.0000947 AC: 1 AN: 10558

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00313 AC: 213 AN: 67974

Other (OTH) AF: 0.0224 AC: 47 AN: 2102

Alfa AF: 0.0142 Hom.: 50

Bravo AF: 0.0249

Asia WGS AF: 0.00606 AC: 22 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00516

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	LPA-related disorder (1)
-	-	1	Myofibrillar myopathy 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.58
DANN	Benign	0.76
PhyloP100		0.29
Mutation Taster		=42/58	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000091
dbscSNV1_RF	Benign	0.024
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: rs41264848; hg19: chr6-160968968;