Genetic Variant ABCC4:c.*879T>C (chr13-95020696-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005845.5(ABCC4):c.*879T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,108 control chromosomes in the GnomAD database, including 13,866 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 0.42 ( 13862 hom., cov: 32)

Exomes 𝑓: 0.65 ( 4 hom. )

Consequence

ABCC4
NM_005845.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.278

Publications

28 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:

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new If you want to explore the variant's impact on the transcript NM_005845.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.*879T>C		3_prime_UTR	Exon 31 of 31	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.*879T>C		3_prime_UTR	Exon 30 of 30	NP_001288758.1	O15439-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCC4	ENST00000645237.2	MANE Select	c.*879T>C	3_prime_UTR	Exon 31 of 31	ENSP00000494609.1	O15439-1
ABCC4	ENST00000903573.1		c.*879T>C	3_prime_UTR	Exon 30 of 30	ENSP00000573632.1
ABCC4	ENST00000932202.1		c.*879T>C	3_prime_UTR	Exon 30 of 30	ENSP00000602261.1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63299

AN:

151970

Hom.:

13861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.407

GnomAD4 exome

AF:

0.650

AC:

AN:

Hom.:

Cov.:

AF XY:

0.571

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.650

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.416

AC:

63302

AN:

152088

Hom.:

13862

Cov.:

AF XY:

0.423

AC XY:

31453

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.288

AC:

11959

AN:

41478

American (AMR)

AF:

0.369

AC:

5634

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

1513

AN:

3472

East Asian (EAS)

AF:

0.494

AC:

2556

AN:

5176

South Asian (SAS)

AF:

0.479

AC:

2315

AN:

4828

European-Finnish (FIN)

AF:

0.603

AC:

6377

AN:

10568

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.464

AC:

31533

AN:

67972

Other (OTH)

AF:

0.405

AC:

853

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1840

3681

5521

7362

9202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.437

Hom.:

43957

Bravo

AF:

0.390

Asia WGS

AF:

0.454

AC:

1579

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

(source)

DANN

Benign

0.60

PhyloP100

0.28

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over