rs11568682

Variant names:

• chr13-95301231-G-A
• rs11568682
• NM_005845.5:c.74+10C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000297451 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.74+10C>T		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.74+10C>T		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.74+10C>T		intron	N/A	NP_001098985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.74+10C>T		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.74+10C>T		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000967420.1		c.74+10C>T		intron	N/A	ENSP00000637479.1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2489 AN: 152076 Hom.: 47 Cov.: 33

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

GnomAD2 exomes AF: 0.0185 AC: 3971 AN: 214578 AF XY: 0.0181

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 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.: 31 AF XY: 0.0208 AC XY: 14770 AN XY: 710684

African (AFR) AF: 0.00243 AC: 74 AN: 30464

American (AMR) AF: 0.00665 AC: 276 AN: 41476

Ashkenazi Jewish (ASJ) AF: 0.00770 AC: 194 AN: 25194

East Asian (EAS) AF: 0.00 AC: 0 AN: 36434

South Asian (SAS) AF: 0.00369 AC: 304 AN: 82380

European-Finnish (FIN) AF: 0.0524 AC: 2709 AN: 51674

Middle Eastern (MID) AF: 0.00299 AC: 17 AN: 5684

European-Non Finnish (NFE) AF: 0.0238 AC: 26084 AN: 1096942

Other (OTH) AF: 0.0169 AC: 995 AN: 58976

GnomAD4 genome AF: 0.0163 AC: 2488 AN: 152184 Hom.: 47 Cov.: 33 AF XY: 0.0170 AC XY: 1268 AN XY: 74404

African (AFR) AF: 0.00363 AC: 151 AN: 41550

American (AMR) AF: 0.00804 AC: 123 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4826

European-Finnish (FIN) AF: 0.0474 AC: 501 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0241 AC: 1635 AN: 67980

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.0190 Hom.: 24

Bravo AF: 0.0127

Asia WGS AF: 0.00261 AC: 9 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.4
DANN	Benign	0.95
PhyloP100		0.084
PromoterAI		-0.0049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11568682; hg19: chr13-95953485;