chr19-1047688-C-G

Variant names:

• chr19-1047688-C-G
• rs4147911
• NM_019112.4:c.2269+34C>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.2269+34C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 1,545,166 control chromosomes in the GnomAD database, including 8,985 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 0.076 (732 hom., cov: 33)
  • Exomes 𝑓: 0.095 (8253 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.2269+34C>G		intron_variant	Intron 16 of 46	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.2269+34C>G		intron_variant	Intron 16 of 46	5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.2949+34C>G		intron_variant	Intron 15 of 43	1
ABCA7	ENST00000533574.1	n.*134C>G		downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11544 AN: 151844 Hom.: 724 Cov.: 33

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.104 AC: 17104 AN: 164352 AF XY: 0.105

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0494

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.343

Gnomad FIN exome AF: 0.0337

Gnomad NFE exome AF: 0.0909

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0952 AC: 132641 AN: 1393206 Hom.: 8253 Cov.: 35 AF XY: 0.0959 AC XY: 65853 AN XY: 686682

African (AFR) AF: 0.0154 AC: 493 AN: 32082

American (AMR) AF: 0.0514 AC: 2035 AN: 39582

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3549 AN: 24780

East Asian (EAS) AF: 0.366 AC: 13551 AN: 37012

South Asian (SAS) AF: 0.114 AC: 9261 AN: 80936

European-Finnish (FIN) AF: 0.0356 AC: 1300 AN: 36484

Middle Eastern (MID) AF: 0.103 AC: 473 AN: 4610

European-Non Finnish (NFE) AF: 0.0889 AC: 96008 AN: 1080040

Other (OTH) AF: 0.104 AC: 5971 AN: 57680

GnomAD4 genome AF: 0.0761 AC: 11559 AN: 151960 Hom.: 732 Cov.: 33 AF XY: 0.0750 AC XY: 5566 AN XY: 74254

African (AFR) AF: 0.0203 AC: 843 AN: 41486

American (AMR) AF: 0.0707 AC: 1080 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3468

East Asian (EAS) AF: 0.318 AC: 1625 AN: 5106

South Asian (SAS) AF: 0.133 AC: 640 AN: 4808

European-Finnish (FIN) AF: 0.0313 AC: 331 AN: 10578

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0893 AC: 6069 AN: 67932

Other (OTH) AF: 0.114 AC: 240 AN: 2108

Alfa AF: 0.0490 Hom.: 78

Bravo AF: 0.0761

Asia WGS AF: 0.223 AC: 774 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-0.63
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: rs4147911; hg19: chr19-1047687;