19-1063444-A-G

Position:

• chr19-1063444-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.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

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 (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.5713-100A>G		intron_variant		ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.5713-100A>G		intron_variant		5	NM_019112.4	ENSP00000263094.6

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

Gnomad4 AFR exome AF: 0.965

Gnomad4 AMR exome AF: 0.902

Gnomad4 ASJ exome AF: 0.815

Gnomad4 EAS exome AF: 0.640

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 0.826

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

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.831

Alfa AF: 0.843 Hom.: 5275

Bravo AF: 0.866

Asia WGS AF: 0.717 AC: 2491 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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