rs4147912

Positions:

• chr19-1049013-A-C
• chr19-1049013-A-T

Variant summary

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

The NM_019112.4(ABCA7):​c.2380+8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,535,590 control chromosomes in the GnomAD database, including 447,163 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47092 hom., cov: 28)
  • Exomes 𝑓: 0.76 (400071 hom.)
• Consequence: ABCA7 NM_019112.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003073
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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 (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.2380+8A>C		splice_region_variant, intron_variant		ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.2380+8A>C		splice_region_variant, intron_variant		5	NM_019112.4	ENSP00000263094	P1
ABCA7	ENST00000433129.6	n.3060+8A>C		splice_region_variant, intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119091 AN: 151644 Hom.: 47045 Cov.: 28

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.796

GnomAD3 exomes AF: 0.796 AC: 158554 AN: 199228 Hom.: 63359 AF XY: 0.795 AC XY: 86640 AN XY: 109028

Gnomad AFR exome AF: 0.836

Gnomad AMR exome AF: 0.896

Gnomad ASJ exome AF: 0.830

Gnomad EAS exome AF: 0.819

Gnomad SAS exome AF: 0.864

Gnomad FIN exome AF: 0.732

Gnomad NFE exome AF: 0.748

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.759 AC: 1049982 AN: 1383828 Hom.: 400071 Cov.: 23 AF XY: 0.762 AC XY: 523708 AN XY: 686834

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.885

Gnomad4 ASJ exome AF: 0.830

Gnomad4 EAS exome AF: 0.838

Gnomad4 SAS exome AF: 0.863

Gnomad4 FIN exome AF: 0.734

Gnomad4 NFE exome AF: 0.740

Gnomad4 OTH exome AF: 0.769

GnomAD4 genome AF: 0.785 AC: 119189 AN: 151762 Hom.: 47092 Cov.: 28 AF XY: 0.787 AC XY: 58381 AN XY: 74154

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.797

Alfa AF: 0.765 Hom.: 24071

Bravo AF: 0.795

Asia WGS AF: 0.839 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.96
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs4147912; hg19: chr19-1049012;