12-122941028-C-A

Variant names:

• chr12-122941028-C-A
• rs4148866
• NM_019625.4:c.1381-33G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019625.4(ABCB9):​c.1381-33G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,434 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ABCB9 NM_019625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64
• Publications: 25 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB9	NM_019625.4	c.1381-33G>T		intron_variant	Intron 7 of 11	ENST00000280560.13	NP_062571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB9	ENST00000280560.13	c.1381-33G>T		intron_variant	Intron 7 of 11	1	NM_019625.4	ENSP00000280560.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1388434 Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1 AN XY: 681394

African (AFR) AF: 0.0000311 AC: 1 AN: 32148

American (AMR) AF: 0.00 AC: 0 AN: 38764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23642

East Asian (EAS) AF: 0.00 AC: 0 AN: 37382

South Asian (SAS) AF: 0.00 AC: 0 AN: 78202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1065504

Other (OTH) AF: 0.00 AC: 0 AN: 57080

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 32596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
DANN	Benign	0.54
PhyloP100		-3.6

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

Other links and lift over

dbSNP: rs4148866; hg19: chr12-123425575;