rs3752232

Positions:

• chr19-1043749-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.097 (1359 hom., cov: 30)
  • Exomes 𝑓: 0.046 (2477 hom.)
• Consequence: ABCA7 NM_019112.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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]

ACMG classification

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/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.955A>G	p.Thr319Ala	missense_variant	10/47	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.955A>G	p.Thr319Ala	missense_variant	10/47	5	NM_019112.4	ENSP00000263094	P1
ABCA7	ENST00000433129.6	n.1635A>G		non_coding_transcript_exon_variant	9/44	1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14673 AN: 151576 Hom.: 1351 Cov.: 30

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

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.: 34 AF XY: 0.0452 AC XY: 32820 AN XY: 726684

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.: 30 AF XY: 0.0958 AC XY: 7099 AN XY: 74126

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	T
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	N
LIST_S2	Benign	0.034	T;.;T
MetaRNN	Benign	0.0039	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.9	N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.29	T
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	T
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

Other links and lift over

dbSNP: rs3752232; hg19: chr19-1043748; COSMIC: COSV54030168; COSMIC: COSV54030168;