Genetic Variant NM_019112.4: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_019112.4:c.-137-60C>T

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