3-183920057-T-C

Variant names:

• chr3-183920057-T-C
• rs562
• NM_005688.4:c.*1243A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005688.4(ABCC5):​c.*1243A>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 0.526 in 152,546 control chromosomes in the GnomAD database, including 21,757 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 0.53 (21713 hom., cov: 33)
  • Exomes 𝑓: 0.44 (44 hom.)
• Consequence: ABCC5 NM_005688.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697
• Publications: 34 publications found

Genes affected

ABCC5 (HGNC:56): (ATP binding cassette subfamily C member 5) The 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 MRP subfamily which is involved in multi-drug resistance. This protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005688.4. 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
	ABCC5	NM_005688.4	MANE Select	c.*1243A>G		3_prime_UTR	Exon 30 of 30	NP_005679.2	O15440-1
	ABCC5	NM_001320032.2		c.*1243A>G		3_prime_UTR	Exon 30 of 30	NP_001306961.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	ENST00000334444.11	TSL:1 MANE Select	c.*1243A>G		3_prime_UTR	Exon 30 of 30	ENSP00000333926.6	O15440-1
	ABCC5	ENST00000898238.1		c.*1243A>G		3_prime_UTR	Exon 30 of 30	ENSP00000568297.1
	ABCC5	ENST00000956865.1		c.*1243A>G		3_prime_UTR	Exon 30 of 30	ENSP00000626924.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80027 AN: 151996 Hom.: 21678 Cov.: 33

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.539

GnomAD4 exome AF: 0.440 AC: 190 AN: 432 Hom.: 44 Cov.: 0 AF XY: 0.431 AC XY: 106 AN XY: 246

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.435 AC: 180 AN: 414

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.583 AC: 7 AN: 12

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.527 AC: 80112 AN: 152114 Hom.: 21713 Cov.: 33 AF XY: 0.519 AC XY: 38579 AN XY: 74358

African (AFR) AF: 0.661 AC: 27415 AN: 41500

American (AMR) AF: 0.486 AC: 7430 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3468

East Asian (EAS) AF: 0.503 AC: 2600 AN: 5168

South Asian (SAS) AF: 0.439 AC: 2118 AN: 4820

European-Finnish (FIN) AF: 0.400 AC: 4234 AN: 10582

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33048 AN: 67986

Other (OTH) AF: 0.543 AC: 1144 AN: 2108

Alfa AF: 0.498 Hom.: 83796

Bravo AF: 0.538

Asia WGS AF: 0.504 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs562; hg19: chr3-183637845;