17-69060142-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080283.4(ABCA9):c.-14+724A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,044 control chromosomes in the GnomAD database, including 19,506 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 0.47 (19506 hom., cov: 32)
• Consequence: ABCA9 NM_080283.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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]

LOC124904051 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA9	NM_080283.4	c.-14+724A>C		intron_variant		ENST00000340001.9
LOC124904051	XR_007065889.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA9	ENST00000340001.9	c.-14+724A>C		intron_variant		1	NM_080283.4	P1
ABCA9	ENST00000495634.5	c.-14+724A>C		intron_variant		1
ABCA9	ENST00000453985.6	c.-14+724A>C		intron_variant		5
ABCA9	ENST00000585714.1	c.-230+724A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70769 AN: 151928 Hom.: 19512 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.465 AC: 70769 AN: 152044 Hom.: 19506 Cov.: 32 AF XY: 0.465 AC XY: 34520 AN XY: 74308

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.484

Alfa AF: 0.413 Hom.: 1352

Bravo AF: 0.445

Asia WGS AF: 0.456 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.8
Dann	Benign	0.53

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: rs11657541; hg19: chr17-67056283;