rs3751333

Variant names:

• chr13-95301363-G-A
• rs3751333
• NM_005845.5:c.-49C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95301363-G-A
• chr13-95301363-G-C
• chr13-95301363-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.-49C>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 5 publications found

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]

ABCC4 Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000297451 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.-49C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_005845.5	c.-49C>T		5_prime_UTR_variant	Exon 1 of 31	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.-49C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 31		NM_005845.5	ENSP00000494609.1
ABCC4	ENST00000645237.2	c.-49C>T		5_prime_UTR_variant	Exon 1 of 31		NM_005845.5	ENSP00000494609.1

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

GnomAD2 exomes AF: 0.0313 AC: 4142 AN: 132286 AF XY: 0.0320

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 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

African (AFR) AF: 0.00435 AC: 123 AN: 28302

American (AMR) AF: 0.0361 AC: 1181 AN: 32678

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 295 AN: 23676

East Asian (EAS) AF: 0.0556 AC: 1826 AN: 32828

South Asian (SAS) AF: 0.0382 AC: 2918 AN: 76478

European-Finnish (FIN) AF: 0.00419 AC: 202 AN: 48204

Middle Eastern (MID) AF: 0.0204 AC: 97 AN: 4756

European-Non Finnish (NFE) AF: 0.0245 AC: 25722 AN: 1051192

Other (OTH) AF: 0.0280 AC: 1570 AN: 56010

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

African (AFR) AF: 0.00496 AC: 206 AN: 41562

American (AMR) AF: 0.0256 AC: 392 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3468

East Asian (EAS) AF: 0.0896 AC: 462 AN: 5156

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4830

European-Finnish (FIN) AF: 0.00341 AC: 36 AN: 10566

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0219 AC: 1484 AN: 67888

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

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
PhyloP100		0.34
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=297/3	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: rs3751333; hg19: chr13-95953617;