rs78117248

Variant names:

• chr19-1052854-A-G
• rs78117248
• NM_019112.4:c.3221-475A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.85).
• 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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.3221-475A>G		intron_variant	Intron 23 of 46	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.3221-475A>G		intron_variant	Intron 23 of 46	5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.3901-475A>G		intron_variant	Intron 22 of 43	1
ABCA7	ENST00000435683.7	n.692-475A>G		intron_variant	Intron 6 of 28	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

African (AFR) AF: 0.00469 AC: 194 AN: 41384

American (AMR) AF: 0.0152 AC: 231 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.00727 AC: 35 AN: 4812

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0227 AC: 1544 AN: 67904

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

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
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs78117248; hg19: chr19-1052853;