rs2292998

Variant names:

• chr3-183946045-T-C
• rs2292998
• NM_005688.4:c.3415-106A>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.3415-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 988,376 control chromosomes in the GnomAD database, including 170,278 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 0.63 (31046 hom., cov: 32)
  • Exomes 𝑓: 0.57 (139232 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.09
• Publications: 17 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 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.3415-106A>G		intron	N/A	NP_005679.2	O15440-1
	ABCC5	NM_001320032.2		c.1999-106A>G		intron	N/A	NP_001306961.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	ENST00000334444.11	TSL:1 MANE Select	c.3415-106A>G		intron	N/A	ENSP00000333926.6	O15440-1
	ABCC5	ENST00000898238.1		c.3415-106A>G		intron	N/A	ENSP00000568297.1
	ABCC5	ENST00000956865.1		c.3415-106A>G		intron	N/A	ENSP00000626924.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95536 AN: 151974 Hom.: 30997 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.570 AC: 476410 AN: 836284 Hom.: 139232 AF XY: 0.569 AC XY: 249735 AN XY: 439260

African (AFR) AF: 0.789 AC: 16961 AN: 21492

American (AMR) AF: 0.531 AC: 22972 AN: 43262

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 12079 AN: 21894

East Asian (EAS) AF: 0.853 AC: 30800 AN: 36112

South Asian (SAS) AF: 0.547 AC: 40110 AN: 73316

European-Finnish (FIN) AF: 0.509 AC: 22262 AN: 43716

Middle Eastern (MID) AF: 0.588 AC: 2669 AN: 4540

European-Non Finnish (NFE) AF: 0.553 AC: 305602 AN: 552270

Other (OTH) AF: 0.578 AC: 22955 AN: 39682

GnomAD4 genome AF: 0.629 AC: 95636 AN: 152092 Hom.: 31046 Cov.: 32 AF XY: 0.623 AC XY: 46292 AN XY: 74336

African (AFR) AF: 0.783 AC: 32520 AN: 41512

American (AMR) AF: 0.586 AC: 8946 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1915 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4414 AN: 5178

South Asian (SAS) AF: 0.561 AC: 2703 AN: 4818

European-Finnish (FIN) AF: 0.501 AC: 5283 AN: 10554

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37915 AN: 67976

Other (OTH) AF: 0.640 AC: 1346 AN: 2102

Alfa AF: 0.574 Hom.: 31178

Bravo AF: 0.642

Asia WGS AF: 0.729 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0050
DANN	Benign	0.32
PhyloP100		-4.1
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: rs2292998; hg19: chr3-183663833; COSMIC: COSV55588287; COSMIC: COSV55588287;