Genetic Variant ABCA7:c.5713-100A>G (chr19-1063444-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019112.4(ABCA7):c.5713-100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,483,286 control chromosomes in the GnomAD database, including 515,304 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 0.86 ( 56701 hom., cov: 29)

Exomes 𝑓: 0.83 ( 458603 hom. )

Consequence

ABCA7
NM_019112.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.35

Publications

154 publications found

Variant links:

Genes affected

ABCA7 (HGNC:37): (ATP binding cassette subfamily A member 7) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This full transporter has been detected predominantly in myelo-lymphatic tissues with the highest expression in peripheral leukocytes, thymus, spleen, and bone marrow. The function of this protein is not yet known; however, the expression pattern suggests a role in lipid homeostasis in cells of the immune system. [provided by RefSeq, Jul 2008]

ABCA7 Gene-Disease associations (from GenCC):

Alzheimer disease 9
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ABCA7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4 link	c.5713-100A>G		intron_variant	Intron 42 of 46	ENST00000263094.11	NP_061985.2	Q8IZY2-1B3KUJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11 link	c.5713-100A>G		intron_variant	Intron 42 of 46	5	NM_019112.4	ENSP00000263094.6		Q8IZY2-1

Frequencies

GnomAD3 genomes

AF:

0.863

AC:

130387

AN:

151120

Hom.:

56645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.957

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.868

Gnomad ASJ

AF:

0.812

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.804

Gnomad FIN

AF:

0.885

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.828

Gnomad OTH

AF:

0.838

GnomAD4 exome

AF:

0.828

AC:

1103321

AN:

1332052

Hom.:

458603

AF XY:

0.828

AC XY:

544400

AN XY:

657444

show subpopulations

African (AFR)

AF:

0.965

AC:

29550

AN:

30618

American (AMR)

AF:

0.902

AC:

32988

AN:

36590

Ashkenazi Jewish (ASJ)

AF:

0.815

AC:

17460

AN:

21432

East Asian (EAS)

AF:

0.640

AC:

24690

AN:

38598

South Asian (SAS)

AF:

0.828

AC:

62517

AN:

75468

European-Finnish (FIN)

AF:

0.884

AC:

32292

AN:

36514

Middle Eastern (MID)

AF:

0.856

AC:

3311

AN:

3870

European-Non Finnish (NFE)

AF:

0.827

AC:

854606

AN:

1033380

Other (OTH)

AF:

0.826

AC:

45907

AN:

55582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9650

19299

28949

38598

48248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.863

AC:

130494

AN:

151234

Hom.:

56701

Cov.:

AF XY:

0.865

AC XY:

63877

AN XY:

73880

show subpopulations

African (AFR)

AF:

0.957

AC:

39423

AN:

41184

American (AMR)

AF:

0.868

AC:

13214

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.812

AC:

2812

AN:

3462

East Asian (EAS)

AF:

0.665

AC:

3387

AN:

5096

South Asian (SAS)

AF:

0.804

AC:

3857

AN:

4796

European-Finnish (FIN)

AF:

0.885

AC:

9251

AN:

10452

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.828

AC:

56062

AN:

67722

Other (OTH)

AF:

0.831

AC:

1743

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

904

1808

2713

3617

4521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.836

Hom.:

13997

Bravo

AF:

0.866

Asia WGS

AF:

0.717

AC:

2491

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.65

(source)

DANN

Benign

0.55

PhyloP100

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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19-1063444-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over