Variant 13-95021685-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005845.5(ABCC4):c.3871-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,533,306 control chromosomes in the GnomAD database, including 735,693 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.94 ( 67639 hom., cov: 30)

Exomes 𝑓: 0.98 ( 668054 hom. )

Consequence

ABCC4
NM_005845.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001400

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ABCC4	NM_005845.5 linkuse as main transcript	c.3871-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000645237.2
ABCC4	NM_001301829.2 linkuse as main transcript	c.3730-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ABCC4	XM_047430034.1 linkuse as main transcript	c.3742-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ABCC4	XM_047430035.1 linkuse as main transcript	c.3322-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2 linkuse as main transcript	c.3871-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_005845.5	P1	O15439-1

Frequencies

GnomAD3 genomes

AF:

0.942

AC:

142463

AN:

151280

Hom.:

67602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.969

Gnomad ASJ

AF:

0.985

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.980

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.950

GnomAD3 exomes

AF:

0.950

AC:

192652

AN:

202836

Hom.:

91565

AF XY:

0.954

AC XY:

104253

AN XY:

109304

show subpopulations

Gnomad AFR exome

AF:

0.768

Gnomad AMR exome

AF:

0.959

Gnomad ASJ exome

AF:

0.959

Gnomad EAS exome

AF:

0.963

Gnomad SAS exome

AF:

0.953

Gnomad FIN exome

AF:

0.979

Gnomad NFE exome

AF:

0.966

Gnomad OTH exome

AF:

0.963

GnomAD4 exome

AF:

0.983

AC:

1358236

AN:

1381908

Hom.:

668054

Cov.:

AF XY:

0.983

AC XY:

676995

AN XY:

688802

show subpopulations

Gnomad4 AFR exome

AF:

0.790

Gnomad4 AMR exome

AF:

0.971

Gnomad4 ASJ exome

AF:

0.977

Gnomad4 EAS exome

AF:

0.985

Gnomad4 SAS exome

AF:

0.971

Gnomad4 FIN exome

AF:

0.989

Gnomad4 NFE exome

AF:

0.990

Gnomad4 OTH exome

AF:

0.974

GnomAD4 genome

AF:

0.942

AC:

142555

AN:

151398

Hom.:

67639

Cov.:

AF XY:

0.943

AC XY:

69778

AN XY:

73968

show subpopulations

Gnomad4 AFR

AF:

0.809

Gnomad4 AMR

AF:

0.969

Gnomad4 ASJ

AF:

0.985

Gnomad4 EAS

AF:

0.991

Gnomad4 SAS

AF:

0.980

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.950

Alfa

AF:

0.971

Hom.:

13142

Bravo

AF:

0.933

Asia WGS

AF:

0.930

AC:

3231

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.3

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over