3-183990651-T-C

Variant names:

• chr3-183990651-T-C
• rs10937158
• NM_005688.4:c.130-1268A>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.130-1268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,930 control chromosomes in the GnomAD database, including 29,642 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 (29642 hom., cov: 32)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 19 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=-0.96).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	NM_005688.4	MANE Select	c.130-1268A>G		intron	N/A	NP_005679.2
	ABCC5	NM_001320032.2		c.-1402-1268A>G		intron	N/A	NP_001306961.1
	ABCC5	NM_001023587.3		c.130-1268A>G		intron	N/A	NP_001018881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	ENST00000334444.11	TSL:1 MANE Select	c.130-1268A>G		intron	N/A	ENSP00000333926.6
	ABCC5	ENST00000427120.6	TSL:1	c.130-1268A>G		intron	N/A	ENSP00000404809.2
	ABCC5	ENST00000392579.6	TSL:1	c.130-1268A>G		intron	N/A	ENSP00000376358.2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93651 AN: 151810 Hom.: 29610 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.617 AC: 93734 AN: 151930 Hom.: 29642 Cov.: 32 AF XY: 0.611 AC XY: 45401 AN XY: 74272

African (AFR) AF: 0.745 AC: 30876 AN: 41436

American (AMR) AF: 0.579 AC: 8846 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1910 AN: 3468

East Asian (EAS) AF: 0.852 AC: 4367 AN: 5128

South Asian (SAS) AF: 0.554 AC: 2670 AN: 4820

European-Finnish (FIN) AF: 0.501 AC: 5290 AN: 10564

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

European-Non Finnish (NFE) AF: 0.557 AC: 37861 AN: 67934

Other (OTH) AF: 0.627 AC: 1324 AN: 2110

Alfa AF: 0.580 Hom.: 65229

Bravo AF: 0.629

Asia WGS AF: 0.708 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.1
DANN	Benign	0.31
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10937158; hg19: chr3-183708439;