17-69060142-T-G

Variant names:

• chr17-69060142-T-G
• rs11657541
• NM_080283.4:c.-14+724A>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.-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
• Publications: 3 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]

ENSG00000300449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.-14+724A>C		intron	N/A	NP_525022.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA9	ENST00000340001.9	TSL:1 MANE Select	c.-14+724A>C		intron	N/A	ENSP00000342216.3
	ABCA9	ENST00000495634.5	TSL:1	c.-14+724A>C		intron	N/A	ENSP00000465601.1
	ABCA9	ENST00000453985.6	TSL:5	c.-14+724A>C		intron	N/A	ENSP00000394264.2

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

African (AFR) AF: 0.158 AC: 6577 AN: 41502

American (AMR) AF: 0.521 AC: 7964 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2037 AN: 3464

East Asian (EAS) AF: 0.324 AC: 1677 AN: 5176

South Asian (SAS) AF: 0.584 AC: 2817 AN: 4820

European-Finnish (FIN) AF: 0.567 AC: 5982 AN: 10546

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41931 AN: 67944

Other (OTH) AF: 0.484 AC: 1023 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		0.10
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: rs11657541; hg19: chr17-67056283;