rs3751333

chr13-95301363-G-Achr13-95301363-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):c.-49C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 1,506,190 control chromosomes in the GnomAD database, including 594 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 0.019 (61 hom., cov: 33)
  • Exomes 𝑓: 0.025 (533 hom.)
• Consequence: ABCC4 NM_005845.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

Genes affected

ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL blood group)) 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 family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

LOC102724149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.-49C>T		5_prime_UTR_variant	1/31	ENST00000645237.2
LOC102724149	XR_429273.4	n.313+100G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.-49C>T		5_prime_UTR_variant	1/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2875 AN: 151958 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.00497

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.00341

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.0313 AC: 4142 AN: 132286 Hom.: 136 AF XY: 0.0320 AC XY: 2332 AN XY: 72840

Gnomad AFR exome AF: 0.00651

Gnomad AMR exome AF: 0.0402

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.0381

Gnomad FIN exome AF: 0.00408

Gnomad NFE exome AF: 0.0252

Gnomad OTH exome AF: 0.0291

GnomAD4 exome AF: 0.0251 AC: 33934 AN: 1354124 Hom.: 533 Cov.: 26 AF XY: 0.0254 AC XY: 17000 AN XY: 670300

Gnomad4 AFR exome AF: 0.00435

Gnomad4 AMR exome AF: 0.0361

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.0556

Gnomad4 SAS exome AF: 0.0382

Gnomad4 FIN exome AF: 0.00419

Gnomad4 NFE exome AF: 0.0245

Gnomad4 OTH exome AF: 0.0280

GnomAD4 genome AF: 0.0189 AC: 2869 AN: 152066 Hom.: 61 Cov.: 33 AF XY: 0.0183 AC XY: 1358 AN XY: 74340

Gnomad4 AFR AF: 0.00496

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.0896

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.00341

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0175 Hom.: 16

Bravo AF: 0.0214

Asia WGS AF: 0.0560 AC: 192 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	12
Dann	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751333; hg19: chr13-95953617;