rs3749438

Variant names:

• chr3-183987396-G-A
• rs3749438
• ENST00000427120.6:c.*269C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-183987396-G-A
• chr3-183987396-G-T

Variant summary

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

The ENST00000427120.6(ABCC5):​c.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 469,754 control chromosomes in the GnomAD database, including 31,859 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 0.33 (8632 hom., cov: 32)
  • Exomes 𝑓: 0.38 (23227 hom.)
• Consequence: ABCC5 ENST00000427120.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.591+374C>T		intron_variant	Intron 5 of 29	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.591+374C>T		intron_variant	Intron 5 of 29	1	NM_005688.4	ENSP00000333926.6

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50277 AN: 151776 Hom.: 8635 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.379 AC: 120529 AN: 317860 Hom.: 23227 Cov.: 0 AF XY: 0.381 AC XY: 62517 AN XY: 163968

African (AFR) AF: 0.269 AC: 2654 AN: 9866

American (AMR) AF: 0.307 AC: 3521 AN: 11474

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 4462 AN: 10888

East Asian (EAS) AF: 0.485 AC: 11912 AN: 24562

South Asian (SAS) AF: 0.398 AC: 8563 AN: 21526

European-Finnish (FIN) AF: 0.299 AC: 6580 AN: 22034

Middle Eastern (MID) AF: 0.421 AC: 651 AN: 1546

European-Non Finnish (NFE) AF: 0.382 AC: 75002 AN: 196186

Other (OTH) AF: 0.363 AC: 7184 AN: 19778

GnomAD4 genome AF: 0.331 AC: 50275 AN: 151894 Hom.: 8632 Cov.: 32 AF XY: 0.326 AC XY: 24187 AN XY: 74220

African (AFR) AF: 0.265 AC: 10985 AN: 41448

American (AMR) AF: 0.304 AC: 4639 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2194 AN: 5166

South Asian (SAS) AF: 0.372 AC: 1788 AN: 4802

European-Finnish (FIN) AF: 0.275 AC: 2896 AN: 10522

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25249 AN: 67924

Other (OTH) AF: 0.344 AC: 726 AN: 2110

Alfa AF: 0.362 Hom.: 20444

Bravo AF: 0.329

Asia WGS AF: 0.387 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.54
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs3749438; hg19: chr3-183705184;