rs2292997

Variant names:

• chr3-184006284-G-A
• rs2292997
• NM_005688.4:c.129+7980C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-184006284-G-A
• chr3-184006284-G-C
• chr3-184006284-G-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.129+7980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 140,368 control chromosomes in the GnomAD database, including 1,336 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 0.13 (1336 hom., cov: 27)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 9 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]

ABCC5-AS1 (HGNC:40055): (ABCC5 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 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.129+7980C>T		intron	N/A	NP_005679.2	O15440-1
	ABCC5	NM_001320032.2		c.-1403+7980C>T		intron	N/A	NP_001306961.1
	ABCC5	NM_001023587.3		c.129+7980C>T		intron	N/A	NP_001018881.1	O15440-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	ENST00000334444.11	TSL:1 MANE Select	c.129+7980C>T		intron	N/A	ENSP00000333926.6	O15440-1
	ABCC5	ENST00000427120.6	TSL:1	c.129+7980C>T		intron	N/A	ENSP00000404809.2	A5PKY6
	ABCC5	ENST00000392579.6	TSL:1	c.129+7980C>T		intron	N/A	ENSP00000376358.2	O15440-2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 18099 AN: 140270 Hom.: 1325 Cov.: 27

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0753

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.129 AC: 18127 AN: 140360 Hom.: 1336 Cov.: 27 AF XY: 0.133 AC XY: 8994 AN XY: 67470

African (AFR) AF: 0.0886 AC: 3225 AN: 36392

American (AMR) AF: 0.205 AC: 2821 AN: 13752

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 264 AN: 3394

East Asian (EAS) AF: 0.360 AC: 1699 AN: 4720

South Asian (SAS) AF: 0.137 AC: 597 AN: 4370

European-Finnish (FIN) AF: 0.138 AC: 1167 AN: 8482

Middle Eastern (MID) AF: 0.0704 AC: 19 AN: 270

European-Non Finnish (NFE) AF: 0.119 AC: 7905 AN: 66174

Other (OTH) AF: 0.143 AC: 272 AN: 1904

Alfa AF: 0.119 Hom.: 3445

Bravo AF: 0.127

Asia WGS AF: 0.239 AC: 831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2292997; hg19: chr3-183724072;