rs3752228

Variant names:

• chr19-1041165-C-T
• rs3752228
• NM_019112.4:c.-137-60C>T

Variant summary

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

The NM_019112.4(ABCA7):​c.-137-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 629,336 control chromosomes in the GnomAD database, including 1,146 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 0.065 (482 hom., cov: 32)
  • Exomes 𝑓: 0.044 (664 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019112.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	NM_019112.4	MANE Select	c.-137-60C>T		intron	N/A	NP_061985.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	ENST00000263094.11	TSL:5 MANE Select	c.-137-60C>T		intron	N/A	ENSP00000263094.6
	ABCA7	ENST00000433129.6	TSL:1	n.201-60C>T		intron	N/A
	ABCA7	ENST00000525238.2	TSL:1	n.80-60C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9885 AN: 152012 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.0551

GnomAD4 exome AF: 0.0444 AC: 21187 AN: 477206 Hom.: 664 Cov.: 5 AF XY: 0.0448 AC XY: 11287 AN XY: 252084

African (AFR) AF: 0.131 AC: 1730 AN: 13224

American (AMR) AF: 0.0238 AC: 549 AN: 23068

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 397 AN: 14386

East Asian (EAS) AF: 0.0715 AC: 2253 AN: 31530

South Asian (SAS) AF: 0.0613 AC: 3028 AN: 49432

European-Finnish (FIN) AF: 0.0275 AC: 862 AN: 31356

Middle Eastern (MID) AF: 0.0199 AC: 40 AN: 2010

European-Non Finnish (NFE) AF: 0.0389 AC: 11102 AN: 285122

Other (OTH) AF: 0.0453 AC: 1226 AN: 27078

GnomAD4 genome AF: 0.0652 AC: 9915 AN: 152130 Hom.: 482 Cov.: 32 AF XY: 0.0648 AC XY: 4822 AN XY: 74364

African (AFR) AF: 0.131 AC: 5417 AN: 41446

American (AMR) AF: 0.0327 AC: 500 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3468

East Asian (EAS) AF: 0.0896 AC: 464 AN: 5176

South Asian (SAS) AF: 0.0638 AC: 308 AN: 4824

European-Finnish (FIN) AF: 0.0298 AC: 317 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0395 AC: 2683 AN: 67992

Other (OTH) AF: 0.0560 AC: 118 AN: 2108

Alfa AF: 0.0480 Hom.: 234

Bravo AF: 0.0681

Asia WGS AF: 0.0850 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.74
PhyloP100		-0.64
PromoterAI		-0.18	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3752228; hg19: chr19-1041164; COSMIC: COSV54036836; COSMIC: COSV54036836;