rs11568684

chr13-95207834-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005845.5(ABCC4):c.877A>G(p.Lys293Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000366 in 1,613,268 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31854674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.877A>G	p.Lys293Glu	missense_variant	7/31	ENST00000645237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.877A>G	p.Lys293Glu	missense_variant	7/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000267 AC: 67 AN: 250582 Hom.: 0 AF XY: 0.000295 AC XY: 40 AN XY: 135438

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000493

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000381 AC: 557 AN: 1461058 Hom.: 0 Cov.: 31 AF XY: 0.000376 AC XY: 273 AN XY: 726828

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000461

Gnomad4 OTH exome AF: 0.000497

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17 AN XY: 74360

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.000419 Hom.: 0

Bravo AF: 0.000276

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000327

EpiControl AF: 0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Pathogenic	0.24
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T;.;.;.;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.7	M;M;M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.58	T
Polyphen		0.37	B;B;B;.;.;.
Vest4		0.55, 0.50, 0.47
MVP		0.86
MPC		0.42
ClinPred		0.13	T
GERP RS		5.5
Varity_R		0.58
gMVP		0.81

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: rs11568684; hg19: chr13-95860088;