19-1046521-T-G

Variant names:

• chr19-1046521-T-G
• rs3764650
• NM_019112.4:c.1622+115T>G

Variant summary

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

The NM_019112.4(ABCA7):​c.1622+115T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,381,032 control chromosomes in the GnomAD database, including 11,058 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 0.15 (2175 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8883 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 220 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	NM_019112.4	MANE Select	c.1622+115T>G		intron	N/A	NP_061985.2	Q8IZY2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	ENST00000263094.11	TSL:5 MANE Select	c.1622+115T>G		intron	N/A	ENSP00000263094.6	Q8IZY2-1
	ABCA7	ENST00000433129.6	TSL:1	n.2302+115T>G		intron	N/A
	ABCA7	ENST00000533574.1	TSL:4	n.263+117T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22044 AN: 151930 Hom.: 2154 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.0926

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.104 AC: 127913 AN: 1228986 Hom.: 8883 AF XY: 0.104 AC XY: 62942 AN XY: 606904

African (AFR) AF: 0.266 AC: 7375 AN: 27676

American (AMR) AF: 0.0695 AC: 1990 AN: 28652

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 2746 AN: 19030

East Asian (EAS) AF: 0.366 AC: 13948 AN: 38106

South Asian (SAS) AF: 0.118 AC: 7951 AN: 67346

European-Finnish (FIN) AF: 0.0369 AC: 1259 AN: 34152

Middle Eastern (MID) AF: 0.116 AC: 417 AN: 3592

European-Non Finnish (NFE) AF: 0.0897 AC: 85984 AN: 958690

Other (OTH) AF: 0.121 AC: 6243 AN: 51742

GnomAD4 genome AF: 0.145 AC: 22103 AN: 152046 Hom.: 2175 Cov.: 33 AF XY: 0.143 AC XY: 10607 AN XY: 74320

African (AFR) AF: 0.262 AC: 10876 AN: 41442

American (AMR) AF: 0.0925 AC: 1414 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3466

East Asian (EAS) AF: 0.320 AC: 1644 AN: 5134

South Asian (SAS) AF: 0.134 AC: 647 AN: 4824

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10612

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0900 AC: 6119 AN: 67970

Other (OTH) AF: 0.161 AC: 339 AN: 2108

Alfa AF: 0.111 Hom.: 4971

Bravo AF: 0.154

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.53
PhyloP100		-0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3764650; hg19: chr19-1046520; COSMIC: COSV54028967; COSMIC: COSV54028967;