Genetic Variant ABCC4:c.1263+70T>C (chr13-95194766-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005845.5(ABCC4):c.1263+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,317,414 control chromosomes in the GnomAD database, including 152,601 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 0.48 ( 17782 hom., cov: 32)

Exomes 𝑓: 0.48 ( 134819 hom. )

Consequence

ABCC4
NM_005845.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0680

Publications

16 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:

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5 link	c.1263+70T>C		intron_variant	Intron 9 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.1263+70T>C		intron_variant	Intron 9 of 30		NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73372

AN:

151884

Hom.:

17781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.475

GnomAD4 exome

AF:

0.480

AC:

559488

AN:

1165412

Hom.:

134819

AF XY:

0.479

AC XY:

279914

AN XY:

584936

show subpopulations

African (AFR)

AF:

0.489

AC:

13194

AN:

26960

American (AMR)

AF:

0.488

AC:

17269

AN:

35422

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

10162

AN:

23182

East Asian (EAS)

AF:

0.518

AC:

19012

AN:

36696

South Asian (SAS)

AF:

0.437

AC:

31717

AN:

72646

European-Finnish (FIN)

AF:

0.513

AC:

26219

AN:

51122

Middle Eastern (MID)

AF:

0.462

AC:

2395

AN:

5184

European-Non Finnish (NFE)

AF:

0.480

AC:

415186

AN:

864074

Other (OTH)

AF:

0.485

AC:

24334

AN:

50126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

13845

27691

41536

55382

69227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11558

23116

34674

46232

57790

<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:

0.483

AC:

73409

AN:

152002

Hom.:

17782

Cov.:

AF XY:

0.482

AC XY:

35841

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.486

AC:

20134

AN:

41398

American (AMR)

AF:

0.470

AC:

7181

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1520

AN:

3472

East Asian (EAS)

AF:

0.512

AC:

2643

AN:

5166

South Asian (SAS)

AF:

0.454

AC:

2186

AN:

4814

European-Finnish (FIN)

AF:

0.524

AC:

5534

AN:

10564

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.478

AC:

32516

AN:

67994

Other (OTH)

AF:

0.471

AC:

995

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1963

3926

5889

7852

9815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.472

Hom.:

28983

Bravo

AF:

0.483

Asia WGS

AF:

0.501

AC:

1743

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

(source)

DANN

Benign

0.68

PhyloP100

0.068

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