dbSNP rs3752228: ABCA7:c.-137-60C>T (chr19-1041165-C-T) – 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.-137-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 629,336 control chromosomes in the GnomAD database, including 1,146 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 0.065 ( 482 hom., cov: 32)

Exomes 𝑓: 0.044 ( 664 hom. )

Consequence

ABCA7
NM_019112.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.644

Publications

11 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 (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4 link	c.-137-60C>T		intron_variant	Intron 1 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.-137-60C>T		intron_variant	Intron 1 of 46	5	NM_019112.4	ENSP00000263094.6		Q8IZY2-1

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9885

AN:

152012

Hom.:

477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.0896

Gnomad SAS

AF:

0.0640

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0395

Gnomad OTH

AF:

0.0551

GnomAD4 exome

AF:

0.0444

AC:

21187

AN:

477206

Hom.:

664

Cov.:

AF XY:

0.0448

AC XY:

11287

AN XY:

252084

show subpopulations

African (AFR)

AF:

0.131

AC:

1730

AN:

13224

American (AMR)

AF:

0.0238

AC:

549

AN:

23068

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

397

AN:

14386

East Asian (EAS)

AF:

0.0715

AC:

2253

AN:

31530

South Asian (SAS)

AF:

0.0613

AC:

3028

AN:

49432

European-Finnish (FIN)

AF:

0.0275

AC:

862

AN:

31356

Middle Eastern (MID)

AF:

0.0199

AC:

AN:

2010

European-Non Finnish (NFE)

AF:

0.0389

AC:

11102

AN:

285122

Other (OTH)

AF:

0.0453

AC:

1226

AN:

27078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1021

2041

3062

4082

5103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0652

AC:

9915

AN:

152130

Hom.:

482

Cov.:

AF XY:

0.0648

AC XY:

4822

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.131

AC:

5417

AN:

41446

American (AMR)

AF:

0.0327

AC:

500

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3468

East Asian (EAS)

AF:

0.0896

AC:

464

AN:

5176

South Asian (SAS)

AF:

0.0638

AC:

308

AN:

4824

European-Finnish (FIN)

AF:

0.0298

AC:

317

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0395

AC:

2683

AN:

67992

Other (OTH)

AF:

0.0560

AC:

118

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

451

901

1352

1802

2253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0480

Hom.:

234

Bravo

AF:

0.0681

Asia WGS

AF:

0.0850

AC:

293

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

(source)

DANN

Benign

0.74

PhyloP100

-0.64

PromoterAI

-0.18

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs3752228

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