chr17-69031729-A-G

Position:

• chr17-69031729-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.1445+379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,984 control chromosomes in the GnomAD database, including 27,801 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 0.59 (27801 hom., cov: 31)
• Consequence: ABCA9 NM_080283.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA9	NM_080283.4	c.1445+379T>C		intron_variant		ENST00000340001.9	NP_525022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA9	ENST00000340001.9	c.1445+379T>C		intron_variant		1	NM_080283.4	ENSP00000342216.3
ABCA9	ENST00000453985.6	c.1445+379T>C		intron_variant		5		ENSP00000394264.2
ABCA9-AS1	ENST00000627453.2	n.238-892A>G		intron_variant		5
ABCA9-AS1	ENST00000629311.1	n.230-892A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89943 AN: 151866 Hom.: 27787 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.592 AC: 89998 AN: 151984 Hom.: 27801 Cov.: 31 AF XY: 0.589 AC XY: 43783 AN XY: 74274

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.595

Alfa AF: 0.668 Hom.: 19953

Bravo AF: 0.578

Asia WGS AF: 0.506 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.62

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: rs7215642; hg19: chr17-67027870;