ENST00000427120.6:c.*269C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000427120.6(ABCC5):​c.*269C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 318,550 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ABCC5 ENST00000427120.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427120.6. 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.591+374C>A		intron	N/A	NP_005679.2
	ABCC5	NM_001320032.2		c.-941+374C>A		intron	N/A	NP_001306961.1
	ABCC5	NM_001023587.3		c.591+374C>A		intron	N/A	NP_001018881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC5	ENST00000427120.6	TSL:1	c.*269C>A		3_prime_UTR	Exon 5 of 5	ENSP00000404809.2
	ABCC5	ENST00000334444.11	TSL:1 MANE Select	c.591+374C>A		intron	N/A	ENSP00000333926.6
	ABCC5	ENST00000392579.6	TSL:1	c.591+374C>A		intron	N/A	ENSP00000376358.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000314 AC: 1 AN: 318550 Hom.: 0 Cov.: 0 AF XY: 0.00000609 AC XY: 1 AN XY: 164298

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9884

American (AMR) AF: 0.00 AC: 0 AN: 11498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10908

East Asian (EAS) AF: 0.00 AC: 0 AN: 24614

South Asian (SAS) AF: 0.0000464 AC: 1 AN: 21574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1548

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 196620

Other (OTH) AF: 0.00 AC: 0 AN: 19812

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.036
DANN	Benign	0.48
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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;