Variant rs11568700 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005845.5(ABCC4):c.185+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,609,654 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 37 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 34 hom. )

Consequence

ABCC4
NM_005845.5 splice_region, intron

Scores

Splicing: ADA: 0.00002608

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.161

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:

ABCC4 (HGNC:):

ABCC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-95247636-G-A is Benign according to our data. Variant chr13-95247636-G-A is described in ClinVar as [Benign]. Clinvar id is 776803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1961/152104) while in subpopulation AFR AF= 0.0441 (1829/41470). AF 95% confidence interval is 0.0424. There are 37 homozygotes in gnomad4. There are 943 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC4	NM_005845.5 linkuse as main transcript	c.185+7C>T		splice_region_variant, intron_variant		ENST00000645237.2	NP_005836.2	O15439-1A8K2Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2 linkuse as main transcript	c.185+7C>T		splice_region_variant, intron_variant			NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1959

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00327

AC:

821

AN:

250832

Hom.:

AF XY:

0.00246

AC XY:

333

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.0438

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00140

AC:

2040

AN:

1457550

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

853

AN XY:

725344

show subpopulations

Gnomad4 AFR exome

AF:

0.0469

Gnomad4 AMR exome

AF:

0.00255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.00319

GnomAD4 genome

AF:

0.0129

AC:

1961

AN:

152104

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

943

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0441

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00615

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.92

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over