Variant rs899494 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005845.5(ABCC4):c.669T>C(p.Ile223Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 1,613,874 control chromosomes in the GnomAD database, including 583,998 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 0.83 ( 52727 hom., cov: 34)

Exomes 𝑓: 0.85 ( 531271 hom. )

Consequence

ABCC4
NM_005845.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

Variant links:

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 links:

ABCC4 (HGNC:):

ABCC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-2.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5 linkuse as main transcript	c.669T>C	p.Ile223Ile	synonymous_variant	6/31	ENST00000645237.2	NP_005836.2	O15439-1A8K2Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2 linkuse as main transcript	c.669T>C	p.Ile223Ile	synonymous_variant	6/31		NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.831

AC:

126405

AN:

152102

Hom.:

52705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.864

Gnomad AMR

AF:

0.855

Gnomad ASJ

AF:

0.759

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.851

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.859

Gnomad OTH

AF:

0.816

GnomAD3 exomes

AF:

0.833

AC:

209004

AN:

251008

Hom.:

87519

AF XY:

0.826

AC XY:

112107

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.798

Gnomad AMR exome

AF:

0.883

Gnomad ASJ exome

AF:

0.736

Gnomad EAS exome

AF:

0.788

Gnomad SAS exome

AF:

0.742

Gnomad FIN exome

AF:

0.853

Gnomad NFE exome

AF:

0.859

Gnomad OTH exome

AF:

0.825

GnomAD4 exome

AF:

0.852

AC:

1244618

AN:

1461654

Hom.:

531271

Cov.:

AF XY:

0.848

AC XY:

616386

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.788

Gnomad4 AMR exome

AF:

0.877

Gnomad4 ASJ exome

AF:

0.744

Gnomad4 EAS exome

AF:

0.792

Gnomad4 SAS exome

AF:

0.748

Gnomad4 FIN exome

AF:

0.852

Gnomad4 NFE exome

AF:

0.867

Gnomad4 OTH exome

AF:

0.833

GnomAD4 genome

AF:

0.831

AC:

126473

AN:

152220

Hom.:

52727

Cov.:

AF XY:

0.828

AC XY:

61608

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.792

Gnomad4 AMR

AF:

0.856

Gnomad4 ASJ

AF:

0.759

Gnomad4 EAS

AF:

0.792

Gnomad4 SAS

AF:

0.747

Gnomad4 FIN

AF:

0.851

Gnomad4 NFE

AF:

0.859

Gnomad4 OTH

AF:

0.809

Alfa

AF:

0.845

Hom.:

94857

Bravo

AF:

0.830

Asia WGS

AF:

0.773

AC:

2690

AN:

3478

EpiCase

AF:

0.848

EpiControl

AF:

0.848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.34

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over