rs3752242

Variant names:

• chr19-1053678-G-A
• rs3752242
• NM_019112.4:c.3424-110G>A

Variant summary

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

The NM_019112.4(ABCA7):​c.3424-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,521,290 control chromosomes in the GnomAD database, including 137,878 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 0.41 (12848 hom., cov: 31)
  • Exomes 𝑓: 0.43 (125030 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.3424-110G>A		intron_variant	Intron 24 of 46	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.3424-110G>A		intron_variant	Intron 24 of 46	5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.4104-110G>A		intron_variant	Intron 23 of 43	1
ABCA7	ENST00000435683.7	n.895-110G>A		intron_variant	Intron 7 of 28	5		ENSP00000465322.2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62034 AN: 151770 Hom.: 12831 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.425 AC: 582321 AN: 1369402 Hom.: 125030 Cov.: 24 AF XY: 0.426 AC XY: 288120 AN XY: 675802

African (AFR) AF: 0.343 AC: 10875 AN: 31706

American (AMR) AF: 0.452 AC: 18357 AN: 40626

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 8450 AN: 22438

East Asian (EAS) AF: 0.355 AC: 13806 AN: 38848

South Asian (SAS) AF: 0.452 AC: 34836 AN: 77022

European-Finnish (FIN) AF: 0.460 AC: 22277 AN: 48404

Middle Eastern (MID) AF: 0.401 AC: 2183 AN: 5446

European-Non Finnish (NFE) AF: 0.427 AC: 447543 AN: 1048084

Other (OTH) AF: 0.422 AC: 23994 AN: 56828

GnomAD4 genome AF: 0.409 AC: 62073 AN: 151888 Hom.: 12848 Cov.: 31 AF XY: 0.412 AC XY: 30607 AN XY: 74246

African (AFR) AF: 0.352 AC: 14580 AN: 41414

American (AMR) AF: 0.438 AC: 6682 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3464

East Asian (EAS) AF: 0.346 AC: 1784 AN: 5154

South Asian (SAS) AF: 0.433 AC: 2078 AN: 4802

European-Finnish (FIN) AF: 0.471 AC: 4986 AN: 10576

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29367 AN: 67910

Other (OTH) AF: 0.417 AC: 877 AN: 2102

Alfa AF: 0.421 Hom.: 49762

Bravo AF: 0.403

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.84
PhyloP100		-0.042
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: rs3752242; hg19: chr19-1053677; COSMIC: COSV54037913; COSMIC: COSV54037913;