rs11568670

Variant names:

• chr13-95186788-C-T
• rs11568670
• NM_005845.5:c.1458G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005845.5(ABCC4):​c.1458G>A​(p.Ser486Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (1 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.919
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 13-95186788-C-T is Benign according to our data. Variant chr13-95186788-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 717558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.919 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.1458G>A	p.Ser486Ser	synonymous	Exon 11 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.1458G>A	p.Ser486Ser	synonymous	Exon 11 of 30	NP_001288758.1
	ABCC4	NM_001105515.3		c.1458G>A	p.Ser486Ser	synonymous	Exon 11 of 21	NP_001098985.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.1458G>A	p.Ser486Ser	synonymous	Exon 11 of 31	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.1458G>A	p.Ser486Ser	synonymous	Exon 11 of 21	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.1458G>A	p.Ser486Ser	synonymous	Exon 11 of 30	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000859 AC: 216 AN: 251360 AF XY: 0.000824

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00137

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00136 AC: 1992 AN: 1461840 Hom.: 1 Cov.: 31 AF XY: 0.00127 AC XY: 922 AN XY: 727222

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00136 AC: 61 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00164 AC: 1824 AN: 1111982

Other (OTH) AF: 0.00144 AC: 87 AN: 60388

GnomAD4 genome AF: 0.000906 AC: 138 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74444

African (AFR) AF: 0.000289 AC: 12 AN: 41544

American (AMR) AF: 0.00111 AC: 17 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00153 AC: 104 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.00113

EpiCase AF: 0.00180

EpiControl AF: 0.00124

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

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: rs11568670; hg19: chr13-95839042;