17-69005427-A-G

Variant names:

• chr17-69005427-A-G
• rs4968828
• NM_080283.4:c.3435+2332T>C

Variant summary

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

The NM_080283.4(ABCA9):​c.3435+2332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,084 control chromosomes in the GnomAD database, including 48,587 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 0.79 (48587 hom., cov: 31)
• Consequence: ABCA9 NM_080283.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44
• Publications: 1 publications found

Genes affected

ABCA9 (HGNC:39): (ATP binding cassette subfamily A member 9) This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two transmembrane domains and two nucleotide binding folds. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This gene is a member of the ABC1 subfamily and is clustered with four other ABC1 family members on chromosome 17q24. Transcriptional expression of this gene is induced during monocyte differentiation into macrophages and is suppressed by cholesterol import. [provided by RefSeq, Jul 2008]

ABCA9-AS1 (HGNC:39983): (ABCA9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080283.4. 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
	ABCA9	NM_080283.4	MANE Select	c.3435+2332T>C		intron	N/A	NP_525022.2
	ABCA9-AS1	NR_126414.1		n.80+634A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA9	ENST00000340001.9	TSL:1 MANE Select	c.3435+2332T>C		intron	N/A	ENSP00000342216.3
	ABCA9	ENST00000453985.6	TSL:5	c.3321+2635T>C		intron	N/A	ENSP00000394264.2
	ABCA9-AS1	ENST00000458677.1	TSL:2	n.80+634A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120210 AN: 151966 Hom.: 48526 Cov.: 31

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.775

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.791 AC: 120336 AN: 152084 Hom.: 48587 Cov.: 31 AF XY: 0.785 AC XY: 58321 AN XY: 74326

African (AFR) AF: 0.949 AC: 39425 AN: 41534

American (AMR) AF: 0.813 AC: 12433 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2736 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2314 AN: 5140

South Asian (SAS) AF: 0.698 AC: 3357 AN: 4810

European-Finnish (FIN) AF: 0.656 AC: 6933 AN: 10566

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50544 AN: 67960

Other (OTH) AF: 0.775 AC: 1636 AN: 2112

Alfa AF: 0.764 Hom.: 68050

Bravo AF: 0.807

Asia WGS AF: 0.623 AC: 2166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.40
PhyloP100		-3.4
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: rs4968828; hg19: chr17-67001568;