chr13-95209550-A-G

Variant summary

Our verdict is Benign. The variant received -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

Publications

38 publications found
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 Gene-Disease associations (from GenCC):
  • qualitative platelet defect
    Inheritance: AR Classification: MODERATE Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
ABCC4NM_005845.5 linkc.669T>C p.Ile223Ile synonymous_variant Exon 6 of 31 ENST00000645237.2 NP_005836.2 O15439-1A8K2Q2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCC4ENST00000645237.2 linkc.669T>C p.Ile223Ile synonymous_variant Exon 6 of 31 NM_005845.5 ENSP00000494609.1 O15439-1

Frequencies

GnomAD3 genomes
AF:
0.831
AC:
126405
AN:
152102
Hom.:
52705
Cov.:
34
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
GnomAD2 exomes
AF:
0.833
AC:
209004
AN:
251008
AF XY:
0.826
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 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.:
47
AF XY:
0.848
AC XY:
616386
AN XY:
727132
show subpopulations
African (AFR)
AF:
0.788
AC:
26388
AN:
33478
American (AMR)
AF:
0.877
AC:
39197
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
0.744
AC:
19427
AN:
26126
East Asian (EAS)
AF:
0.792
AC:
31442
AN:
39686
South Asian (SAS)
AF:
0.748
AC:
64494
AN:
86238
European-Finnish (FIN)
AF:
0.852
AC:
45505
AN:
53416
Middle Eastern (MID)
AF:
0.716
AC:
4127
AN:
5764
European-Non Finnish (NFE)
AF:
0.867
AC:
963716
AN:
1111854
Other (OTH)
AF:
0.833
AC:
50322
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
9443
18886
28328
37771
47214
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
21264
42528
63792
85056
106320
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.831
AC:
126473
AN:
152220
Hom.:
52727
Cov.:
34
AF XY:
0.828
AC XY:
61608
AN XY:
74450
show subpopulations
African (AFR)
AF:
0.792
AC:
32893
AN:
41518
American (AMR)
AF:
0.856
AC:
13087
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.759
AC:
2633
AN:
3468
East Asian (EAS)
AF:
0.792
AC:
4110
AN:
5188
South Asian (SAS)
AF:
0.747
AC:
3600
AN:
4820
European-Finnish (FIN)
AF:
0.851
AC:
9027
AN:
10604
Middle Eastern (MID)
AF:
0.782
AC:
230
AN:
294
European-Non Finnish (NFE)
AF:
0.859
AC:
58394
AN:
68008
Other (OTH)
AF:
0.809
AC:
1711
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1138
2277
3415
4554
5692
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
886
1772
2658
3544
4430
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.846
Hom.:
212233
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
PhyloP100
-2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs899494; hg19: chr13-95861804; COSMIC: COSV65316381; API