dbSNP rs3752232: ABCA7:p.Thr319Ala (chr19-1043749-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019112.4(ABCA7):c.955A>G(p.Thr319Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,612,638 control chromosomes in the GnomAD database, including 3,836 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.097 ( 1359 hom., cov: 30)

Exomes 𝑓: 0.046 ( 2477 hom. )

Consequence

ABCA7
NM_019112.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003932923).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4 link	c.955A>G	p.Thr319Ala	missense_variant	Exon 10 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.955A>G	p.Thr319Ala	missense_variant	Exon 10 of 47	5	NM_019112.4	ENSP00000263094.6		Q8IZY2-1
ABCA7	ENST00000433129.6 link	n.1635A>G		non_coding_transcript_exon_variant	Exon 9 of 44	1

Frequencies

GnomAD3 genomes

AF:

0.0968

AC:

14673

AN:

151576

Hom.:

1351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0289

Gnomad EAS

AF:

0.0898

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0399

Gnomad OTH

AF:

0.0703

GnomAD3 exomes

AF:

0.0548

AC:

13709

AN:

250038

Hom.:

752

AF XY:

0.0513

AC XY:

6935

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0241

Gnomad ASJ exome

AF:

0.0277

Gnomad EAS exome

AF:

0.0862

Gnomad SAS exome

AF:

0.0512

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0403

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0459

AC:

67112

AN:

1460944

Hom.:

2477

Cov.:

AF XY:

0.0452

AC XY:

32820

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.0738

Gnomad4 SAS exome

AF:

0.0501

Gnomad4 FIN exome

AF:

0.0276

Gnomad4 NFE exome

AF:

0.0402

Gnomad4 OTH exome

AF:

0.0544

GnomAD4 genome

AF:

0.0970

AC:

14719

AN:

151694

Hom.:

1359

Cov.:

AF XY:

0.0958

AC XY:

7099

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.0413

Gnomad4 ASJ

AF:

0.0289

Gnomad4 EAS

AF:

0.0898

Gnomad4 SAS

AF:

0.0525

Gnomad4 FIN

AF:

0.0300

Gnomad4 NFE

AF:

0.0399

Gnomad4 OTH

AF:

0.0715

Alfa

AF:

0.0468

Hom.:

647

Bravo

AF:

0.105

TwinsUK

AF:

0.0464

AC:

172

ALSPAC

AF:

0.0423

AC:

163

ESP6500AA

AF:

0.254

AC:

1119

ESP6500EA

AF:

0.0408

AC:

351

ExAC

AF:

0.0599

AC:

7276

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

EpiCase

AF:

0.0366

EpiControl

AF:

0.0349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.0

DANN

Benign

0.62

DEOGEN2

Benign

0.098

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.034

T;.;T

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.9

N;N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

1.0

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.88

T;T;.

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.0080

MPC

0.10

ClinPred

0.0000096

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over