Genetic Variant ABCC4:p.Val345Val (chr13-95206658-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_005845.5(ABCC4):c.1035G>A(p.Val345Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,614,168 control chromosomes in the GnomAD database, including 31 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 0.0045 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 24 hom. )

Consequence

ABCC4
NM_005845.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.362

Publications

5 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 -9 ACMG points.

BP4

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

BP7

Synonymous conserved (PhyloP=-0.362 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5 link	c.1035G>A	p.Val345Val	synonymous_variant	Exon 8 of 31	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2 link	c.1035G>A	p.Val345Val	synonymous_variant	Exon 8 of 31		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes

AF:

0.00451

AC:

686

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00517

AC:

1300

AN:

251374

AF XY:

0.00556

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00306

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0147

Gnomad NFE exome

AF:

0.00492

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00428

AC:

6254

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

3207

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.00313

AC:

140

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

322

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00460

AC:

397

AN:

86250

European-Finnish (FIN)

AF:

0.0132

AC:

703

AN:

53420

Middle Eastern (MID)

AF:

0.0140

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00386

AC:

4296

AN:

1112006

Other (OTH)

AF:

0.00475

AC:

287

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

388

777

1165

1554

1942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<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:

0.00449

AC:

684

AN:

152288

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41552

American (AMR)

AF:

0.00712

AC:

109

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0151

AC:

160

AN:

10616

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00478

AC:

325

AN:

68030

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00460

Hom.:

Bravo

AF:

0.00334

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00567

EpiControl

AF:

0.00415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.9

(source)

DANN

Benign

0.72

PhyloP100

-0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=97/3

polymorphism

(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