rs3752246

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_019112.4(ABCA7):c.4580G>C(p.Gly1527Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,612,048 control chromosomes in the GnomAD database, including 559,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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 ( 57037 hom., cov: 31)

Exomes 𝑓: 0.83 ( 502125 hom. )

Consequence

ABCA7
NM_019112.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.147

Publications

184 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=1.3769012E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019112.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	NM_019112.4	MANE Select	c.4580G>C	p.Gly1527Ala	missense	Exon 33 of 47	NP_061985.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA7	ENST00000263094.11	TSL:5 MANE Select	c.4580G>C	p.Gly1527Ala	missense	Exon 33 of 47	ENSP00000263094.6
ABCA7	ENST00000433129.6	TSL:1	n.4880G>C		non_coding_transcript_exon	Exon 30 of 44
ABCA7	ENST00000435683.7	TSL:5	n.*463G>C		non_coding_transcript_exon	Exon 16 of 29	ENSP00000465322.2

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

131155

AN:

152064

Hom.:

56979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.957

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.868

Gnomad ASJ

AF:

0.811

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.807

Gnomad FIN

AF:

0.885

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.827

Gnomad OTH

AF:

0.839

GnomAD2 exomes

AF:

0.840

AC:

207104

AN:

246680

AF XY:

0.836

show subpopulations

Gnomad AFR exome

AF:

0.962

Gnomad AMR exome

AF:

0.904

Gnomad ASJ exome

AF:

0.809

Gnomad EAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.885

Gnomad NFE exome

AF:

0.830

Gnomad OTH exome

AF:

0.836

GnomAD4 exome

AF:

0.828

AC:

1208802

AN:

1459866

Hom.:

502125

Cov.:

AF XY:

0.828

AC XY:

601248

AN XY:

726214

show subpopulations

African (AFR)

AF:

0.964

AC:

32249

AN:

33456

American (AMR)

AF:

0.899

AC:

40118

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.812

AC:

21204

AN:

26114

East Asian (EAS)

AF:

0.642

AC:

25457

AN:

39642

South Asian (SAS)

AF:

0.834

AC:

71860

AN:

86184

European-Finnish (FIN)

AF:

0.885

AC:

46204

AN:

52234

Middle Eastern (MID)

AF:

0.855

AC:

4934

AN:

5768

European-Non Finnish (NFE)

AF:

0.825

AC:

916947

AN:

1111496

Other (OTH)

AF:

0.826

AC:

49829

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

11853

23706

35558

47411

59264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20954

41908

62862

83816

104770

<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:

0.863

AC:

131264

AN:

152182

Hom.:

57037

Cov.:

AF XY:

0.864

AC XY:

64277

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.957

AC:

39753

AN:

41520

American (AMR)

AF:

0.868

AC:

13260

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.811

AC:

2813

AN:

3468

East Asian (EAS)

AF:

0.666

AC:

3439

AN:

5166

South Asian (SAS)

AF:

0.807

AC:

3887

AN:

4818

European-Finnish (FIN)

AF:

0.885

AC:

9380

AN:

10600

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.827

AC:

56226

AN:

68010

Other (OTH)

AF:

0.831

AC:

1756

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

898

1795

2693

3590

4488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.842

Hom.:

12149

Bravo

AF:

0.865

TwinsUK

AF:

0.815

AC:

3021

ALSPAC

AF:

0.828

AC:

3190

ESP6500AA

AF:

0.956

AC:

4214

ESP6500EA

AF:

0.829

AC:

7127

ExAC

AF:

0.838

AC:

101568

Asia WGS

AF:

0.727

AC:

2530

AN:

3478

EpiCase

AF:

0.828

EpiControl

AF:

0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.67

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.15

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0000014

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

PhyloP100

-0.15

PrimateAI

Benign

0.43

PROVEAN

Benign

2.7

REVEL

Benign

0.18

Sift

Benign

0.88

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.013

MPC

0.11

ClinPred

0.000015

GERP RS

1.6

PromoterAI

0.078

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.16

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over