12-122941028-C-T

Position:

• chr12-122941028-C-T

Variant summary

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

The NM_019625.4(ABCB9):​c.1381-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,539,396 control chromosomes in the GnomAD database, including 133,128 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 0.34 (10681 hom., cov: 32)
  • Exomes 𝑓: 0.41 (122447 hom.)
• Consequence: ABCB9 NM_019625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB9	NM_019625.4	c.1381-33G>A		intron_variant		ENST00000280560.13	NP_062571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB9	ENST00000280560.13	c.1381-33G>A		intron_variant		1	NM_019625.4	ENSP00000280560	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51293 AN: 151892 Hom.: 10685 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.430 AC: 82952 AN: 192864 Hom.: 18779 AF XY: 0.439 AC XY: 45459 AN XY: 103616

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.427

Gnomad EAS exome AF: 0.679

Gnomad SAS exome AF: 0.521

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.435

GnomAD4 exome AF: 0.413 AC: 573588 AN: 1387386 Hom.: 122447 Cov.: 33 AF XY: 0.417 AC XY: 283798 AN XY: 680806

Gnomad4 AFR exome AF: 0.0892

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.337 AC: 51292 AN: 152010 Hom.: 10681 Cov.: 32 AF XY: 0.344 AC XY: 25567 AN XY: 74292

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.367

Alfa AF: 0.387 Hom.: 13291

Bravo AF: 0.324

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.62

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: rs4148866; hg19: chr12-123425575; COSMIC: COSV54890802; COSMIC: COSV54890802;