rs11568658

chr13-95210754-C-A

Variant summary

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

The NM_005845.5(ABCC4):c.559G>T(p.Gly187Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0308 in 1,613,498 control chromosomes in the GnomAD database, including 1,431 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.032 (161 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1270 hom.)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052810013).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.559G>T	p.Gly187Trp	missense_variant	5/31	ENST00000645237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.559G>T	p.Gly187Trp	missense_variant	5/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4849 AN: 152130 Hom.: 162 Cov.: 32

Gnomad AFR AF: 0.00478

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0387

GnomAD3 exomes AF: 0.0490 AC: 12291 AN: 251012 Hom.: 509 AF XY: 0.0474 AC XY: 6431 AN XY: 135702

Gnomad AFR exome AF: 0.00462

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.0405

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.0620

Gnomad FIN exome AF: 0.0400

Gnomad NFE exome AF: 0.0233

Gnomad OTH exome AF: 0.0433

GnomAD4 exome AF: 0.0307 AC: 44919 AN: 1461250 Hom.: 1270 Cov.: 31 AF XY: 0.0316 AC XY: 22972 AN XY: 726946

Gnomad4 AFR exome AF: 0.00397

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.0612

Gnomad4 FIN exome AF: 0.0381

Gnomad4 NFE exome AF: 0.0219

Gnomad4 OTH exome AF: 0.0311

GnomAD4 genome AF: 0.0318 AC: 4846 AN: 152248 Hom.: 161 Cov.: 32 AF XY: 0.0355 AC XY: 2643 AN XY: 74430

Gnomad4 AFR AF: 0.00477

Gnomad4 AMR AF: 0.0871

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0285 Hom.: 246

Bravo AF: 0.0356

TwinsUK AF: 0.0191 AC: 71

ALSPAC AF: 0.0221 AC: 85

ESP6500AA AF: 0.00635 AC: 28

ESP6500EA AF: 0.0228 AC: 196

ExAC AF: 0.0447 AC: 5430

Asia WGS AF: 0.0720 AC: 249 AN: 3478

EpiCase AF: 0.0263

EpiControl AF: 0.0277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	0.020
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D;.;.;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0053	T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.6	H;H;H;.;H;.
MutationTaster	Benign	0.0000020	P;P;P;P
PrimateAI	Uncertain	0.53	T
Polyphen		1.0	D;D;D;.;.;.
Vest4		0.18, 0.35, 0.36
MPC		0.85
ClinPred		0.086	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.69

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: rs11568658; hg19: chr13-95863008; COSMIC: COSV65310023;