17-69005427-A-G

Position:

• chr17-69005427-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA9	NM_080283.4	c.3435+2332T>C		intron_variant		ENST00000340001.9	NP_525022.2
ABCA9-AS1	NR_126414.1	n.80+634A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA9	ENST00000340001.9	c.3435+2332T>C		intron_variant		1	NM_080283.4	ENSP00000342216	P1
ABCA9-AS1	ENST00000630625.1	n.378-6556A>G		intron_variant, non_coding_transcript_variant		5
ABCA9	ENST00000453985.6	c.3321+2635T>C		intron_variant		5		ENSP00000394264
ABCA9-AS1	ENST00000458677.1	n.80+634A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.775

Alfa AF: 0.756 Hom.: 51092

Bravo AF: 0.807

Asia WGS AF: 0.623 AC: 2166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs4968828; hg19: chr17-67001568;