Variant 13-95206524-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005845.5(ABCC4):c.1161+8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,611,314 control chromosomes in the GnomAD database, including 263 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 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.016 ( 242 hom. )

Consequence

ABCC4
NM_005845.5 splice_region, intron

Scores

Splicing: ADA: 0.001266

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.126

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0126 (1914/152270) while in subpopulation NFE AF= 0.0207 (1408/68018). AF 95% confidence interval is 0.0198. There are 21 homozygotes in gnomad4. There are 913 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5 linkuse as main transcript	c.1161+8T>A		splice_region_variant, intron_variant		ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2 linkuse as main transcript	c.1161+8T>A		splice_region_variant, intron_variant			NM_005845.5	ENSP00000494609	P1	O15439-1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1914

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0126

AC:

3169

AN:

250776

Hom.:

AF XY:

0.0126

AC XY:

1709

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00507

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.0224

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.0160

AC:

23309

AN:

1459044

Hom.:

242

Cov.:

AF XY:

0.0159

AC XY:

11522

AN XY:

725186

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00551

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00242

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0184

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0126

AC:

1914

AN:

152270

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

913

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.0230

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0183

EpiControl

AF:

0.0171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.79

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.016

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