chr19-1042810-A-G

Position:

• chr19-1042810-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019112.4(ABCA7):​c.563A>G​(p.Glu188Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,608,896 control chromosomes in the GnomAD database, including 184,990 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (14587 hom., cov: 33)
  • Exomes 𝑓: 0.48 (170403 hom.)
• Consequence: ABCA7 NM_019112.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.58

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5857913E-6).
• BP6: Variant 19-1042810-A-G is Benign according to our data. Variant chr19-1042810-A-G is described in ClinVar as [Benign]. Clinvar id is 1237748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA7	NM_019112.4	c.563A>G	p.Glu188Gly	missense_variant	7/47	ENST00000263094.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA7	ENST00000263094.11	c.563A>G	p.Glu188Gly	missense_variant	7/47	5	NM_019112.4	P1
ABCA7	ENST00000433129.6	n.1243A>G		non_coding_transcript_exon_variant	6/44	1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63529 AN: 151950 Hom.: 14576 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.496 AC: 122416 AN: 246568 Hom.: 32209 AF XY: 0.495 AC XY: 66327 AN XY: 133984

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.710

Gnomad ASJ exome AF: 0.503

Gnomad EAS exome AF: 0.428

Gnomad SAS exome AF: 0.516

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.474

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.479 AC: 697589 AN: 1456826 Hom.: 170403 Cov.: 54 AF XY: 0.481 AC XY: 348479 AN XY: 724882

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.468

GnomAD4 genome AF: 0.418 AC: 63566 AN: 152070 Hom.: 14587 Cov.: 33 AF XY: 0.423 AC XY: 31422 AN XY: 74306

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.426

Alfa AF: 0.467 Hom.: 16554

Bravo AF: 0.417

TwinsUK AF: 0.471 AC: 1747

ALSPAC AF: 0.468 AC: 1802

ESP6500AA AF: 0.222 AC: 979

ESP6500EA AF: 0.474 AC: 4076

ExAC AF: 0.481 AC: 58401

Asia WGS AF: 0.457 AC: 1589 AN: 3478

EpiCase AF: 0.475

EpiControl AF: 0.472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 22, 2019	This variant is associated with the following publications: (PMID: 31182772, 30917570) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.5
DANN	Benign	0.81
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.56	T;.;T
MetaRNN	Benign	0.0000056	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L;L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.87	N;N;.
REVEL	Benign	0.15
Sift	Benign	0.65	T;T;.
Sift4G	Benign	0.40	T;T;T
Polyphen		0.24	B;B;B
Vest4		0.056
MPC		0.12
ClinPred		0.0020	T
GERP RS		-0.62
Varity_R		0.044
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3764645; hg19: chr19-1042809; COSMIC: COSV54025202; COSMIC: COSV54025202;