rs11077858

chr17-68975434-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA9	NM_080283.4	c.*481C>G		3_prime_UTR_variant	39/39	ENST00000340001.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA9	ENST00000340001.9	c.*481C>G		3_prime_UTR_variant	39/39	1	NM_080283.4	P1
ABCA9-AS1	ENST00000630625.1	n.377+30527G>C		intron_variant, non_coding_transcript_variant		5
ABCA9	ENST00000453985.6	c.*481C>G		3_prime_UTR_variant	38/38	5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.763

Gnomad4 NFE exome AF: 0.713

Gnomad4 OTH exome AF: 0.929

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

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.497

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.7
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs11077858; hg19: chr17-66971575;