rs1468050109

Variant names:

• chr13-95071817-G-A
• rs1468050109
• NM_005845.5:c.3055C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95071817-G-A
• chr13-95071817-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005845.5(ABCC4):​c.3055C>T​(p.Leu1019Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.47

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3055C>T	p.Leu1019Phe	missense_variant	Exon 25 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.2914C>T	p.Leu972Phe	missense_variant	Exon 24 of 30		NP_001288758.1
ABCC4	XM_047430034.1	c.2926C>T	p.Leu976Phe	missense_variant	Exon 25 of 31		XP_047285990.1
ABCC4	XM_047430035.1	c.2506C>T	p.Leu836Phe	missense_variant	Exon 22 of 28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3055C>T	p.Leu1019Phe	missense_variant	Exon 25 of 31		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Pathogenic	4.0	H;H;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.9	.;D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	.;D;.
Sift4G	Uncertain	0.0030	.;D;.
Polyphen		0.98	D;D;D
Vest4		0.37
MutPred		0.44		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;
MVP		0.81
MPC		0.81
ClinPred		1.0	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
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: rs1468050109; hg19: chr13-95724071;