dbSNP rs11568682: ABCC4:c.74+10C>T (chr13-95301231-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005845.5(ABCC4):c.74+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,581,408 control chromosomes in the GnomAD database, including 447 homozygotes. 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 0.016 ( 47 hom., cov: 33)

Exomes 𝑓: 0.021 ( 400 hom. )

Consequence

ABCC4
NM_005845.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0840

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:

LOC102724149 (HGNC:):

LOC102724149 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=-0.79).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2488/152184) while in subpopulation NFE AF= 0.0241 (1635/67980). AF 95% confidence interval is 0.0231. There are 47 homozygotes in gnomad4. There are 1268 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5 link	c.74+10C>T		intron_variant	Intron 1 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.74+10C>T		intron_variant	Intron 1 of 30		NM_005845.5	ENSP00000494609.1		O15439-1

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2489

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0474

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0185

AC:

3971

AN:

214578

Hom.:

AF XY:

0.0181

AC XY:

2134

AN XY:

118118

show subpopulations

Gnomad AFR exome

AF:

0.00361

Gnomad AMR exome

AF:

0.00699

Gnomad ASJ exome

AF:

0.00681

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00403

Gnomad FIN exome

AF:

0.0523

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0214

AC:

30653

AN:

1429224

Hom.:

400

Cov.:

AF XY:

0.0208

AC XY:

14770

AN XY:

710684

show subpopulations

Gnomad4 AFR exome

AF:

0.00243

Gnomad4 AMR exome

AF:

0.00665

Gnomad4 ASJ exome

AF:

0.00770

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00369

Gnomad4 FIN exome

AF:

0.0524

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0163

AC:

2488

AN:

152184

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1268

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00363

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0474

Gnomad4 NFE

AF:

0.0241

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0127

Asia WGS

AF:

0.00261

AC:

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.4

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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