17-68975434-G-C

Variant names:

• chr17-68975434-G-C
• rs11077858
• NM_080283.4:c.*481C>G

Variant summary

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

The NM_080283.4(ABCA9):​c.*481C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,464 control chromosomes in the GnomAD database, including 21,820 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 0.49 (21687 hom., cov: 32)
  • Exomes 𝑓: 0.71 (133 hom.)
• Consequence: ABCA9 NM_080283.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 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.*481C>G		3_prime_UTR	Exon 39 of 39	NP_525022.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA9	ENST00000340001.9	TSL:1 MANE Select	c.*481C>G		3_prime_UTR	Exon 39 of 39	ENSP00000342216.3
	ABCA9	ENST00000453985.6	TSL:5	c.*481C>G		3_prime_UTR	Exon 38 of 38	ENSP00000394264.2
	ABCA9-AS1	ENST00000630625.1	TSL:5	n.377+30527G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74479 AN: 151858 Hom.: 21691 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.711 AC: 347 AN: 488 Hom.: 133 Cov.: 0 AF XY: 0.679 AC XY: 159 AN XY: 234

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.671 AC: 55 AN: 82

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.763 AC: 29 AN: 38

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.713 AC: 248 AN: 348

Other (OTH) AF: 0.929 AC: 13 AN: 14

GnomAD4 genome AF: 0.490 AC: 74484 AN: 151976 Hom.: 21687 Cov.: 32 AF XY: 0.491 AC XY: 36456 AN XY: 74270

African (AFR) AF: 0.164 AC: 6778 AN: 41434

American (AMR) AF: 0.544 AC: 8305 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2174 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1706 AN: 5168

South Asian (SAS) AF: 0.580 AC: 2792 AN: 4812

European-Finnish (FIN) AF: 0.631 AC: 6665 AN: 10560

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.650 AC: 44160 AN: 67960

Other (OTH) AF: 0.497 AC: 1051 AN: 2114

Alfa AF: 0.571 Hom.: 3370

Bravo AF: 0.465

Asia WGS AF: 0.452 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.87
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11077858; hg19: chr17-66971575;