rs675

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000482.4(APOA4):c.1099A>T(p.Thr367Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,684 control chromosomes in the GnomAD database, including 27,179 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T367A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2071 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25108 hom. )

Consequence

APOA4
NM_000482.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.211

Publications

69 publications found

Variant links:

Genes affected

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 links:

ENSG00000285513 (HGNC:):

ENSG00000285513 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 (MetaRNN=0.001034677).

BP6

Variant 11-116820959-T-A is Benign according to our data. Variant chr11-116820959-T-A is described in ClinVar as Benign. ClinVar VariationId is 1245704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA4	NM_000482.4 link	c.1099A>T	p.Thr367Ser	missense_variant	Exon 3 of 3	ENST00000357780.5	NP_000473.2	P06727

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOA4	ENST00000357780.5 link	c.1099A>T	p.Thr367Ser	missense_variant	Exon 3 of 3	1	NM_000482.4	ENSP00000350425.3	P06727
ENSG00000285513	ENST00000645414.1 link	n.169-61T>A		intron_variant	Intron 1 of 1
ENSG00000305923	ENST00000814126.1 link	n.135+6619T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23864

AN:

151724

Hom.:

2072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.168

GnomAD2 exomes

AF:

0.150

AC:

37745

AN:

251308

AF XY:

0.155

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0941

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.000652

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.180

AC:

262873

AN:

1461840

Hom.:

25108

Cov.:

AF XY:

0.180

AC XY:

130631

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.113

AC:

3782

AN:

33480

American (AMR)

AF:

0.100

AC:

4470

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

5569

AN:

26136

East Asian (EAS)

AF:

0.000353

AC:

AN:

39698

South Asian (SAS)

AF:

0.134

AC:

11526

AN:

86254

European-Finnish (FIN)

AF:

0.142

AC:

7580

AN:

53408

Middle Eastern (MID)

AF:

0.243

AC:

1400

AN:

5768

European-Non Finnish (NFE)

AF:

0.196

AC:

217970

AN:

1111984

Other (OTH)

AF:

0.175

AC:

10562

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

14306

28612

42919

57225

71531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7366

14732

22098

29464

36830

<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:

0.157

AC:

23881

AN:

151844

Hom.:

2071

Cov.:

AF XY:

0.154

AC XY:

11402

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.116

AC:

4812

AN:

41386

American (AMR)

AF:

0.132

AC:

2019

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

765

AN:

3466

East Asian (EAS)

AF:

0.00213

AC:

AN:

5160

South Asian (SAS)

AF:

0.120

AC:

575

AN:

4810

European-Finnish (FIN)

AF:

0.136

AC:

1437

AN:

10530

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13636

AN:

67910

Other (OTH)

AF:

0.165

AC:

348

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1056

2112

3167

4223

5279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.169

Hom.:

1478

Bravo

AF:

0.154

TwinsUK

AF:

0.201

AC:

745

ALSPAC

AF:

0.201

AC:

775

ESP6500AA

AF:

0.113

AC:

496

ESP6500EA

AF:

0.197

AC:

1693

ExAC

AF:

0.150

AC:

18255

EpiCase

AF:

0.201

EpiControl

AF:

0.202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 1349197, 23096082, 12676816, 20117098) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.6

(source)

DANN

Benign

0.40

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

MetaRNN

Benign

0.0010

MetaSVM

Benign

-1.1

PhyloP100

-0.21

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.030

REVEL

Benign

0.023

Sift

Benign

0.50

Sift4G

Benign

0.79

Vest4

0.022

MutPred

0.13

Loss of methylation at K366 (P = 0.1326);

MPC

0.049

ClinPred

0.00030

GERP RS

0.012

gMVP

0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over