rs4147918

Variant names:

Variant summary

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

The NM_019112.4(ABCA7):c.5057A>G(p.Gln1686Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,613,750 control chromosomes in the GnomAD database, including 1,989 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 179 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1810 hom. )

Consequence

ABCA7
NM_019112.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.573

Publications

45 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013472438).

BP6

Variant 19-1058177-A-G is Benign according to our data. Variant chr19-1058177-A-G is described in ClinVar as Benign. ClinVar VariationId is 1246709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4 link	c.5057A>G	p.Gln1686Arg	missense_variant	Exon 37 of 47	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.5057A>G	p.Gln1686Arg	missense_variant	Exon 37 of 47	5	NM_019112.4	ENSP00000263094.6		Q8IZY2-1

Frequencies

GnomAD3 genomes

AF:

0.0354

AC:

5370

AN:

151868

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00745

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.0637

Gnomad FIN

AF:

0.0594

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0405

Gnomad OTH

AF:

0.0274

GnomAD2 exomes

AF:

0.0478

AC:

11991

AN:

251102

AF XY:

0.0491

show subpopulations

Gnomad AFR exome

AF:

0.00665

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.166

Gnomad FIN exome

AF:

0.0582

Gnomad NFE exome

AF:

0.0413

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

AF:

0.0438

AC:

63973

AN:

1461762

Hom.:

1810

Cov.:

AF XY:

0.0442

AC XY:

32121

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.00603

AC:

202

AN:

33480

American (AMR)

AF:

0.0133

AC:

593

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

738

AN:

26136

East Asian (EAS)

AF:

0.147

AC:

5843

AN:

39696

South Asian (SAS)

AF:

0.0622

AC:

5369

AN:

86256

European-Finnish (FIN)

AF:

0.0558

AC:

2974

AN:

53318

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0409

AC:

45448

AN:

1112000

Other (OTH)

AF:

0.0451

AC:

2723

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3988

7976

11965

15953

19941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1810

3620

5430

7240

9050

<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:

0.0353

AC:

5372

AN:

151988

Hom.:

179

Cov.:

AF XY:

0.0372

AC XY:

2767

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00743

AC:

308

AN:

41468

American (AMR)

AF:

0.0207

AC:

316

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

103

AN:

3468

East Asian (EAS)

AF:

0.173

AC:

890

AN:

5148

South Asian (SAS)

AF:

0.0638

AC:

307

AN:

4812

European-Finnish (FIN)

AF:

0.0594

AC:

627

AN:

10562

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0405

AC:

2753

AN:

67988

Other (OTH)

AF:

0.0290

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

247

494

741

988

1235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0394

Hom.:

353

Bravo

AF:

0.0309

TwinsUK

AF:

0.0456

AC:

169

ALSPAC

AF:

0.0449

AC:

173

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.0413

AC:

355

ExAC

AF:

0.0478

AC:

5798

Asia WGS

AF:

0.107

AC:

371

AN:

3478

EpiCase

AF:

0.0370

EpiControl

AF:

0.0354

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 22, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31182772, 30917570) -

ABCA7-related disorder

Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.8

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.21

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.58

T;.;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.23

N;N;.

PhyloP100

-0.57

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.44

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.23

T;T;.

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.025

MPC

0.11

ClinPred

0.00077

GERP RS

-4.3

Varity_R

0.062

gMVP

0.54

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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