rs3764647

Positions:

• chr19-1044713-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.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. 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 0.094 (1240 hom., cov: 31)
  • Exomes 𝑓: 0.046 (2355 hom.)
• Consequence: ABCA7 NM_019112.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.1184A>G	p.His395Arg	missense_variant	11/47	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.1184A>G	p.His395Arg	missense_variant	11/47	5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.1864A>G		non_coding_transcript_exon_variant	10/44	1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14237 AN: 151766 Hom.: 1232 Cov.: 31

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

GnomAD3 exomes AF: 0.0534 AC: 13089 AN: 245046 Hom.: 653 AF XY: 0.0504 AC XY: 6726 AN XY: 133424

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 SAS exome AF: 0.0513

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.: 29 AF XY: 0.0450 AC XY: 32649 AN XY: 725774

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.0276

Gnomad4 EAS exome AF: 0.0737

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.0273

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.0538

GnomAD4 genome AF: 0.0940 AC: 14280 AN: 151880 Hom.: 1240 Cov.: 31 AF XY: 0.0929 AC XY: 6899 AN XY: 74252

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.0400

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.0909

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0496 Hom.: 486

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	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.24
DANN	Benign	0.81
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.070	T;.;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.2	N;N;.
PrimateAI	Benign	0.28	T
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	T
GERP RS		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.60

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: rs3764647; hg19: chr19-1044712; COSMIC: COSV54029595; COSMIC: COSV54029595;