12-122929802-T-C

Variant names:

• chr12-122929802-T-C
• rs2270788
• NM_019625.4:c.*109A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB9	NM_019625.4	MANE Select	c.*109A>G		3_prime_UTR	Exon 12 of 12	NP_062571.1
	ABCB9	NM_001437843.1		c.*109A>G		3_prime_UTR	Exon 12 of 12	NP_001424772.1
	ABCB9	NM_001438398.1		c.*109A>G		3_prime_UTR	Exon 11 of 11	NP_001425327.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB9	ENST00000280560.13	TSL:1 MANE Select	c.*109A>G		3_prime_UTR	Exon 12 of 12	ENSP00000280560.8
	ABCB9	ENST00000542678.5	TSL:1	c.*109A>G		3_prime_UTR	Exon 12 of 12	ENSP00000440288.1
	ABCB9	ENST00000442833.6	TSL:1	c.2040+2390A>G		intron	N/A	ENSP00000456375.1

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

African (AFR) AF: 0.622 AC: 17813 AN: 28636

American (AMR) AF: 0.138 AC: 2718 AN: 19692

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 1321 AN: 18704

East Asian (EAS) AF: 0.208 AC: 7372 AN: 35392

South Asian (SAS) AF: 0.156 AC: 9618 AN: 61790

European-Finnish (FIN) AF: 0.0951 AC: 2965 AN: 31176

Middle Eastern (MID) AF: 0.118 AC: 418 AN: 3536

European-Non Finnish (NFE) AF: 0.0984 AC: 100978 AN: 1025798

Other (OTH) AF: 0.144 AC: 7646 AN: 53100

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

African (AFR) AF: 0.601 AC: 24886 AN: 41432

American (AMR) AF: 0.160 AC: 2440 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1050 AN: 5154

South Asian (SAS) AF: 0.162 AC: 780 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1066 AN: 10594

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0976 AC: 6630 AN: 67956

Other (OTH) AF: 0.214 AC: 452 AN: 2108

Alfa AF: 0.130 Hom.: 6267

Bravo AF: 0.271

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.73
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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