chr12-122930091-C-A

Variant names:

• chr12-122930091-C-A
• rs370679674
• NM_019625.4:c.2121G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_019625.4(ABCB9):​c.2121G>T​(p.Ala707Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000426 in 1,407,930 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. Synonymous variant affecting the same amino acid position (i.e. A707A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ABCB9 NM_019625.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 1 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-2.39 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB9	NM_019625.4	MANE Select	c.2121G>T	p.Ala707Ala	synonymous	Exon 12 of 12	NP_062571.1	Q9NP78-1
	ABCB9	NM_001437843.1		c.2121G>T	p.Ala707Ala	synonymous	Exon 12 of 12	NP_001424772.1
	ABCB9	NM_001438398.1		c.1992G>T	p.Ala664Ala	synonymous	Exon 11 of 11	NP_001425327.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB9	ENST00000280560.13	TSL:1 MANE Select	c.2121G>T	p.Ala707Ala	synonymous	Exon 12 of 12	ENSP00000280560.8	Q9NP78-1
	ABCB9	ENST00000542678.5	TSL:1	c.2121G>T	p.Ala707Ala	synonymous	Exon 12 of 12	ENSP00000440288.1	Q9NP78-1
	ABCB9	ENST00000442833.6	TSL:1	c.2040+2101G>T		intron	N/A	ENSP00000456375.1	Q9NP78-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000426 AC: 6 AN: 1407930 Hom.: 0 Cov.: 34 AF XY: 0.00000431 AC XY: 3 AN XY: 695360

African (AFR) AF: 0.00 AC: 0 AN: 32170

American (AMR) AF: 0.00 AC: 0 AN: 36462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25222

East Asian (EAS) AF: 0.00 AC: 0 AN: 36544

South Asian (SAS) AF: 0.00 AC: 0 AN: 79818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000553 AC: 6 AN: 1084282

Other (OTH) AF: 0.00 AC: 0 AN: 58354

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-2.4

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: rs370679674; hg19: chr12-123414638;