Genetic Variant APOA4:c.*68_*71delTGTC (chr11-116820795-GGACA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000482.4(APOA4):c.*68_*71delTGTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,577,418 control chromosomes in the GnomAD database, including 197,947 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 13398 hom., cov: 0)

Exomes 𝑓: 0.50 ( 184549 hom. )

Consequence

APOA4
NM_000482.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.937

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-116820795-GGACA-G is Benign according to our data. Variant chr11-116820795-GGACA-G is described in ClinVar as [Benign]. Clinvar id is 1238294.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA4	NM_000482.4 link	c.68_71delTGTC		3_prime_UTR_variant	Exon 3 of 3	ENST00000357780.5	NP_000473.2	P06727

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOA4	ENST00000357780.5 link	c.68_71delTGTC	3_prime_UTR_variant	Exon 3 of 3	1	NM_000482.4	ENSP00000350425.3	P06727
ENSG00000285513	ENST00000645414.1 link	n.165_168delACAG	splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000305923	ENST00000814126.1 link	n.135+6469_135+6472delACAG	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58724

AN:

151762

Hom.:

13406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.406

GnomAD4 exome

AF:

0.500

AC:

712397

AN:

1425540

Hom.:

184549

AF XY:

0.494

AC XY:

348997

AN XY:

705810

show subpopulations

African (AFR)

AF:

0.122

AC:

4011

AN:

32758

American (AMR)

AF:

0.473

AC:

20073

AN:

42396

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

9804

AN:

23874

East Asian (EAS)

AF:

0.270

AC:

10661

AN:

39414

South Asian (SAS)

AF:

0.319

AC:

25812

AN:

80896

European-Finnish (FIN)

AF:

0.467

AC:

21964

AN:

47056

Middle Eastern (MID)

AF:

0.346

AC:

1490

AN:

4312

European-Non Finnish (NFE)

AF:

0.540

AC:

591478

AN:

1095972

Other (OTH)

AF:

0.460

AC:

27104

AN:

58862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16705

33410

50116

66821

83526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.387

AC:

58715

AN:

151878

Hom.:

13398

Cov.:

AF XY:

0.381

AC XY:

28251

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.141

AC:

5838

AN:

41500

American (AMR)

AF:

0.433

AC:

6604

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1411

AN:

3464

East Asian (EAS)

AF:

0.292

AC:

1503

AN:

5150

South Asian (SAS)

AF:

0.312

AC:

1503

AN:

4814

European-Finnish (FIN)

AF:

0.457

AC:

4818

AN:

10548

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35511

AN:

67832

Other (OTH)

AF:

0.404

AC:

852

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1654

3307

4961

6614

8268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.313

Hom.:

889

Bravo

AF:

0.382

Asia WGS

AF:

0.276

AC:

963

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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11-116820795-GGACA-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over