dbSNP rs5090: ENSG00000305923:n.136-4826C>G (chr11-116823339-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000814126.1(ENSG00000305923):n.136-4826C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 943,090 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 172 hom., cov: 33)

Exomes 𝑓: 0.048 ( 1159 hom. )

Consequence

ENSG00000305923
ENST00000814126.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.470

Publications

8 publications found

Variant links:

COSMIC-nc: COSV63360462

Genes affected

ENSG00000305923 (HGNC:):

ENSG00000305923 links:

APOA4 (HGNC:602): (apolipoprotein A4) Apoliprotein (apo) A-IV gene contains 3 exons separated by two introns. A sequence polymorphism has been identified in the 3'UTR of the third exon. The primary translation product is a 396-residue preprotein which after proteolytic processing is secreted its primary site of synthesis, the intestine, in association with chylomicron particles. Although its precise function is not known, apo A-IV is a potent activator of lecithin-cholesterol acyltransferase in vitro. [provided by RefSeq, Jul 2008]

APOA4 Gene-Disease associations (from GenCC):

autosomal dominant medullary cystic kidney disease with or without hyperuricemia
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

APOA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-116823339-C-G is Benign according to our data. Variant chr11-116823339-C-G is described in ClinVar as Benign. ClinVar VariationId is 1286717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000814126.1. 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
	APOA4	NM_000482.4	MANE Select	c.-148G>C		upstream_gene	N/A	NP_000473.2	P06727

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000305923	ENST00000814126.1		n.136-4826C>G		intron	N/A
	APOA4	ENST00000357780.5	TSL:1 MANE Select	c.-148G>C		upstream_gene	N/A	ENSP00000350425.3	P06727

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5977

AN:

152204

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00967

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0585

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0614

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.0481

AC:

38008

AN:

790768

Hom.:

1159

Cov.:

AF XY:

0.0471

AC XY:

19623

AN XY:

416796

show subpopulations

African (AFR)

AF:

0.00865

AC:

179

AN:

20702

American (AMR)

AF:

0.0244

AC:

985

AN:

40444

Ashkenazi Jewish (ASJ)

AF:

0.0448

AC:

946

AN:

21102

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35938

South Asian (SAS)

AF:

0.0138

AC:

975

AN:

70498

European-Finnish (FIN)

AF:

0.0604

AC:

2821

AN:

46688

Middle Eastern (MID)

AF:

0.0341

AC:

115

AN:

3376

European-Non Finnish (NFE)

AF:

0.0588

AC:

30237

AN:

514062

Other (OTH)

AF:

0.0461

AC:

1749

AN:

37958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1874

3749

5623

7498

9372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

582

1164

1746

2328

2910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0392

AC:

5977

AN:

152322

Hom.:

172

Cov.:

AF XY:

0.0385

AC XY:

2868

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00964

AC:

401

AN:

41582

American (AMR)

AF:

0.0304

AC:

465

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

158

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.0116

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0585

AC:

621

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0615

AC:

4180

AN:

68022

Other (OTH)

AF:

0.0303

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

302

604

907

1209

1511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0507

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.0

(source)

DANN

Benign

0.62

PhyloP100

0.47

PromoterAI

0.014

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over