dbSNP rs11568682: ABCC4:c.74+10C>T (chr13-95301231-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005845.5(ABCC4):c.74+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,581,408 control chromosomes in the GnomAD database, including 447 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 0.016 ( 47 hom., cov: 33)

Exomes 𝑓: 0.021 ( 400 hom. )

Consequence

ABCC4
NM_005845.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0840

Publications

3 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

ABCC4 links:

ENSG00000297451 (HGNC:):

ENSG00000297451 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0163 (2488/152184) while in subpopulation NFE AF = 0.0241 (1635/67980). AF 95% confidence interval is 0.0231. There are 47 homozygotes in GnomAd4. There are 1268 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5 link	c.74+10C>T		intron_variant	Intron 1 of 30	ENST00000645237.2	NP_005836.2	O15439-1A8K2Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2 link	c.74+10C>T		intron_variant	Intron 1 of 30		NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2489

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0474

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.0185

AC:

3971

AN:

214578

AF XY:

0.0181

show subpopulations

Gnomad AFR exome

AF:

0.00361

Gnomad AMR exome

AF:

0.00699

Gnomad ASJ exome

AF:

0.00681

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0523

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0214

AC:

30653

AN:

1429224

Hom.:

400

Cov.:

AF XY:

0.0208

AC XY:

14770

AN XY:

710684

show subpopulations

African (AFR)

AF:

0.00243

AC:

AN:

30464

American (AMR)

AF:

0.00665

AC:

276

AN:

41476

Ashkenazi Jewish (ASJ)

AF:

0.00770

AC:

194

AN:

25194

East Asian (EAS)

AF:

0.00

AC:

AN:

36434

South Asian (SAS)

AF:

0.00369

AC:

304

AN:

82380

European-Finnish (FIN)

AF:

0.0524

AC:

2709

AN:

51674

Middle Eastern (MID)

AF:

0.00299

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0238

AC:

26084

AN:

1096942

Other (OTH)

AF:

0.0169

AC:

995

AN:

58976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1353

2706

4058

5411

6764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

972

1944

2916

3888

4860

<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:

0.0163

AC:

2488

AN:

152184

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1268

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.00363

AC:

151

AN:

41550

American (AMR)

AF:

0.00804

AC:

123

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00456

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0474

AC:

501

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0241

AC:

1635

AN:

67980

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

127

253

380

506

633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0190

Hom.:

Bravo

AF:

0.0127

Asia WGS

AF:

0.00261

AC:

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.4

(source)

DANN

Benign

0.95

PhyloP100

0.084

PromoterAI

-0.0049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over