chr12-122963381-T-C

Position:

• chr12-122963381-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.-88+2906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,062 control chromosomes in the GnomAD database, including 27,134 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 0.55 (27134 hom., cov: 31)
• Consequence: ABCB9 NM_019625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB9	NM_019625.4	c.-88+2906A>G		intron_variant		ENST00000280560.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB9	ENST00000280560.13	c.-88+2906A>G		intron_variant		1	NM_019625.4	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82964 AN: 151944 Hom.: 27140 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 82956 AN: 152062 Hom.: 27134 Cov.: 31 AF XY: 0.549 AC XY: 40844 AN XY: 74330

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.578

Alfa AF: 0.679 Hom.: 64738

Bravo AF: 0.519

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.82

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: rs4275659; hg19: chr12-123447928;