dbSNP rs2274403: ABCC4:c.1263+70T>G (chr13-95194766-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005845.5(ABCC4):c.1263+70T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,944 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Failed GnomAD Quality Control

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

8.56e-7

AC:

AN:

1168752

Hom.:

AF XY:

0.00000170

AC XY:

AN XY:

586512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27046

American (AMR)

AF:

0.00

AC:

AN:

35502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23240

East Asian (EAS)

AF:

0.00

AC:

AN:

36744

South Asian (SAS)

AF:

0.00

AC:

AN:

72798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5190

European-Non Finnish (NFE)

AF:

0.00000115

AC:

AN:

866772

Other (OTH)

AF:

0.00

AC:

AN:

50270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41296

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

28983

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.89

(source)

DANN

Benign

0.66

PhyloP100

0.068

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over