rs2270788

Positions:

• chr12-122929802-T-C

Variant summary

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

The NM_019625.4(ABCB9):​c.*109A>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 0.132 in 1,429,832 control chromosomes in the GnomAD database, including 21,843 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 0.25 (8392 hom., cov: 31)
  • Exomes 𝑓: 0.12 (13451 hom.)
• Consequence: ABCB9 NM_019625.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459

Genes affected

ABCB9 (HGNC:50): (ATP binding cassette subfamily B member 9) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This family member functions in the translocation of peptides from the cytosol into the lysosomal lumen. Alternative splicing of this gene results in distinct isoforms which are likely to have different substrate specificities. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB9	NM_019625.4	c.*109A>G		3_prime_UTR_variant	12/12	ENST00000280560.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB9	ENST00000280560.13	c.*109A>G		3_prime_UTR_variant	12/12	1	NM_019625.4	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37556 AN: 151890 Hom.: 8348 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.118 AC: 150849 AN: 1277824 Hom.: 13451 Cov.: 34 AF XY: 0.118 AC XY: 72743 AN XY: 617896

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0706

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0951

Gnomad4 NFE exome AF: 0.0984

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.248 AC: 37666 AN: 152008 Hom.: 8392 Cov.: 31 AF XY: 0.245 AC XY: 18179 AN XY: 74334

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0976

Gnomad4 OTH AF: 0.214

Alfa AF: 0.120 Hom.: 3385

Bravo AF: 0.271

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.73

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: rs2270788; hg19: chr12-123414349; COSMIC: COSV54893683; COSMIC: COSV54893683;