dbSNP rs3764647: ABCA7:p.His395Arg (chr19-1044713-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.1184A>G(p.His395Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,610,724 control chromosomes in the GnomAD database, including 3,595 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 0.094 ( 1240 hom., cov: 31)

Exomes 𝑓: 0.046 ( 2355 hom. )

Consequence

ABCA7
NM_019112.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.14

Publications

32 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=0.0030278862).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4 link	c.1184A>G	p.His395Arg	missense_variant	Exon 11 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.1184A>G	p.His395Arg	missense_variant	Exon 11 of 47	5	NM_019112.4	ENSP00000263094.6		Q8IZY2-1
ABCA7	ENST00000433129.6 link	n.1864A>G		non_coding_transcript_exon_variant	Exon 10 of 44	1

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14237

AN:

151766

Hom.:

1232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0402

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.0909

Gnomad SAS

AF:

0.0531

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0401

Gnomad OTH

AF:

0.0696

GnomAD2 exomes

AF:

0.0534

AC:

13089

AN:

245046

AF XY:

0.0504

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.0855

Gnomad FIN exome

AF:

0.0280

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0361

GnomAD4 exome

AF:

0.0457

AC:

66645

AN:

1458844

Hom.:

2355

Cov.:

AF XY:

0.0450

AC XY:

32649

AN XY:

725774

show subpopulations

African (AFR)

AF:

0.239

AC:

7933

AN:

33226

American (AMR)

AF:

0.0258

AC:

1149

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

720

AN:

26086

East Asian (EAS)

AF:

0.0737

AC:

2926

AN:

39680

South Asian (SAS)

AF:

0.0500

AC:

4311

AN:

86152

European-Finnish (FIN)

AF:

0.0273

AC:

1414

AN:

51780

Middle Eastern (MID)

AF:

0.0176

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.0404

AC:

44853

AN:

1111550

Other (OTH)

AF:

0.0538

AC:

3241

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3801

7602

11402

15203

19004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0940

AC:

14280

AN:

151880

Hom.:

1240

Cov.:

AF XY:

0.0929

AC XY:

6899

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.234

AC:

9638

AN:

41206

American (AMR)

AF:

0.0400

AC:

612

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3472

East Asian (EAS)

AF:

0.0909

AC:

470

AN:

5172

South Asian (SAS)

AF:

0.0533

AC:

257

AN:

4818

European-Finnish (FIN)

AF:

0.0300

AC:

318

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0401

AC:

2725

AN:

68010

Other (OTH)

AF:

0.0709

AC:

149

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

622

1245

1867

2490

3112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0550

Hom.:

955

Bravo

AF:

0.100

TwinsUK

AF:

0.0448

AC:

166

ALSPAC

AF:

0.0418

AC:

161

ESP6500AA

AF:

0.240

AC:

1054

ESP6500EA

AF:

0.0405

AC:

348

ExAC

AF:

0.0576

AC:

6953

Asia WGS

AF:

0.0870

AC:

301

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.24

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.070

T;.;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

N;N;.

PhyloP100

-2.1

PrimateAI

Benign

0.28

PROVEAN

Benign

0.11

N;N;.

REVEL

Benign

0.18

Sift

Benign

1.0

T;T;.

Sift4G

Benign

0.69

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.044

MPC

0.13

ClinPred

0.0014

GERP RS

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.60

Mutation Taster

=99/1

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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rs3764647

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