19-1063444-A-G

Variant names:

• chr19-1063444-A-G
• rs4147929
• NM_019112.4:c.5713-100A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019112.4(ABCA7):​c.5713-100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,483,286 control chromosomes in the GnomAD database, including 515,304 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 0.86 (56701 hom., cov: 29)
  • Exomes 𝑓: 0.83 (458603 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 154 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019112.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	NM_019112.4	MANE Select	c.5713-100A>G		intron	N/A	NP_061985.2	Q8IZY2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	ENST00000263094.11	TSL:5 MANE Select	c.5713-100A>G		intron	N/A	ENSP00000263094.6	Q8IZY2-1
	ABCA7	ENST00000433129.6	TSL:1	n.6013-100A>G		intron	N/A
	ABCA7	ENST00000525073.6	TSL:2	c.1045-100A>G		intron	N/A	ENSP00000432031.2	H0YCN5

Frequencies

GnomAD3 genomes AF: 0.863 AC: 130387 AN: 151120 Hom.: 56645 Cov.: 29

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.838

GnomAD4 exome AF: 0.828 AC: 1103321 AN: 1332052 Hom.: 458603 AF XY: 0.828 AC XY: 544400 AN XY: 657444

African (AFR) AF: 0.965 AC: 29550 AN: 30618

American (AMR) AF: 0.902 AC: 32988 AN: 36590

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 17460 AN: 21432

East Asian (EAS) AF: 0.640 AC: 24690 AN: 38598

South Asian (SAS) AF: 0.828 AC: 62517 AN: 75468

European-Finnish (FIN) AF: 0.884 AC: 32292 AN: 36514

Middle Eastern (MID) AF: 0.856 AC: 3311 AN: 3870

European-Non Finnish (NFE) AF: 0.827 AC: 854606 AN: 1033380

Other (OTH) AF: 0.826 AC: 45907 AN: 55582

GnomAD4 genome AF: 0.863 AC: 130494 AN: 151234 Hom.: 56701 Cov.: 29 AF XY: 0.865 AC XY: 63877 AN XY: 73880

African (AFR) AF: 0.957 AC: 39423 AN: 41184

American (AMR) AF: 0.868 AC: 13214 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2812 AN: 3462

East Asian (EAS) AF: 0.665 AC: 3387 AN: 5096

South Asian (SAS) AF: 0.804 AC: 3857 AN: 4796

European-Finnish (FIN) AF: 0.885 AC: 9251 AN: 10452

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56062 AN: 67722

Other (OTH) AF: 0.831 AC: 1743 AN: 2098

Alfa AF: 0.836 Hom.: 13997

Bravo AF: 0.866

Asia WGS AF: 0.717 AC: 2491 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.55
PhyloP100		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4147929; hg19: chr19-1063443; COSMIC: COSV54037963; COSMIC: COSV54037963;