dbSNP rs11568696: ABCC4:c.1825-7A>G (chr13-95166374-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005845.5(ABCC4):c.1825-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,607,130 control chromosomes in the GnomAD database, including 31 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 0.0072 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 18 hom. )

Consequence

ABCC4
NM_005845.5 splice_region, intron

Scores

Splicing: ADA: 0.00003710

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.92

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 -14 ACMG points.

BP4

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

BP6

Variant 13-95166374-T-C is Benign according to our data. Variant chr13-95166374-T-C is described in ClinVar as [Benign]. Clinvar id is 717315.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-95166374-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00719 (1095/152296) while in subpopulation AFR AF= 0.0251 (1043/41570). AF 95% confidence interval is 0.0238. There are 13 homozygotes in gnomad4. There are 516 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5 link	c.1825-7A>G		splice_region_variant, intron_variant	Intron 14 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.1825-7A>G		splice_region_variant, intron_variant	Intron 14 of 30		NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.00718

AC:

1093

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00174

AC:

430

AN:

247608

Hom.:

AF XY:

0.00132

AC XY:

177

AN XY:

134180

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.000996

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000666

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000535

Gnomad OTH exome

AF:

0.000836

GnomAD4 exome

AF:

0.000733

AC:

1066

AN:

1454834

Hom.:

Cov.:

AF XY:

0.000648

AC XY:

469

AN XY:

723984

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000702

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.00168

GnomAD4 genome

AF:

0.00719

AC:

1095

AN:

152296

Hom.:

Cov.:

AF XY:

0.00693

AC XY:

516

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00377

Hom.:

Bravo

AF:

0.00841

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.1

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.0

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