rs2313212

Variant names:

• chr3-183983140-A-G
• rs2313212
• NM_005688.4:c.592-133T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-183983140-A-G
• chr3-183983140-A-T

Variant summary

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

The NM_005688.4(ABCC5):​c.592-133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 773,806 control chromosomes in the GnomAD database, including 134,717 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 0.62 (30462 hom., cov: 33)
  • Exomes 𝑓: 0.57 (104255 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.592-133T>C		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.592-133T>C		intron_variant	Intron 5 of 29	1	NM_005688.4	ENSP00000333926.6
ABCC5	ENST00000265586.10	c.592-133T>C		intron_variant	Intron 5 of 28	5		ENSP00000265586.6
ABCC5	ENST00000437205.5	n.592-133T>C		intron_variant	Intron 5 of 29	5		ENSP00000403510.1
ABCC5	ENST00000492216.1	n.143-133T>C		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94781 AN: 152052 Hom.: 30418 Cov.: 33

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.573 AC: 356042 AN: 621636 Hom.: 104255 AF XY: 0.571 AC XY: 183795 AN XY: 321948

African (AFR) AF: 0.766 AC: 12320 AN: 16078

American (AMR) AF: 0.546 AC: 13481 AN: 24696

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 8728 AN: 15890

East Asian (EAS) AF: 0.854 AC: 27286 AN: 31964

South Asian (SAS) AF: 0.543 AC: 28560 AN: 52562

European-Finnish (FIN) AF: 0.511 AC: 18822 AN: 36810

Middle Eastern (MID) AF: 0.608 AC: 1436 AN: 2360

European-Non Finnish (NFE) AF: 0.554 AC: 226957 AN: 409514

Other (OTH) AF: 0.581 AC: 18452 AN: 31762

GnomAD4 genome AF: 0.623 AC: 94876 AN: 152170 Hom.: 30462 Cov.: 33 AF XY: 0.618 AC XY: 45939 AN XY: 74384

African (AFR) AF: 0.766 AC: 31805 AN: 41520

American (AMR) AF: 0.583 AC: 8915 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4408 AN: 5170

South Asian (SAS) AF: 0.555 AC: 2672 AN: 4818

European-Finnish (FIN) AF: 0.501 AC: 5308 AN: 10588

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37917 AN: 67998

Other (OTH) AF: 0.637 AC: 1346 AN: 2114

Alfa AF: 0.581 Hom.: 82710

Bravo AF: 0.635

Asia WGS AF: 0.725 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.47
PhyloP100		-0.015
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: rs2313212; hg19: chr3-183700928;