rs78117248

Positions:

• chr19-1052854-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_019112.4(ABCA7):​c.3221-475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 151,900 control chromosomes in the GnomAD database, including 37 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 0.015 (37 hom., cov: 30)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2274/151900) while in subpopulation NFE AF= 0.0227 (1544/67904). AF 95% confidence interval is 0.0218. There are 37 homozygotes in gnomad4. There are 1000 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.3221-475A>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.3221-475A>G		intron_variant		5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.3901-475A>G		intron_variant		1
ABCA7	ENST00000435683.7	n.692-475A>G		intron_variant		5		ENSP00000465322.2

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2278 AN: 151782 Hom.: 37 Cov.: 30

Gnomad AFR AF: 0.00473

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00727

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0150 AC: 2274 AN: 151900 Hom.: 37 Cov.: 30 AF XY: 0.0135 AC XY: 1000 AN XY: 74226

Gnomad4 AFR AF: 0.00469

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00727

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0203 Hom.: 10

Bravo AF: 0.0159

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs78117248; hg19: chr19-1052853;