rs11568704

chr13-95034701-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_005845.5(ABCC4):c.3774G>A(p.Pro1258=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,614,154 control chromosomes in the GnomAD database, including 48 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 0.0099 (31 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (17 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.86

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-4.86 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00992 (1510/152282) while in subpopulation AFR AF= 0.0341 (1419/41562). AF 95% confidence interval is 0.0327. There are 31 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.3774G>A	p.Pro1258=	synonymous_variant	30/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.3633G>A	p.Pro1211=	synonymous_variant	29/30
ABCC4	XM_047430034.1	c.3645G>A	p.Pro1215=	synonymous_variant	30/31
ABCC4	XM_047430035.1	c.3225G>A	p.Pro1075=	synonymous_variant	27/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.3774G>A	p.Pro1258=	synonymous_variant	30/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes AF: 0.00983 AC: 1496 AN: 152164 Hom.: 30 Cov.: 33

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

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: 0.000221

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00259 AC: 650 AN: 251418 Hom.: 8 AF XY: 0.00198 AC XY: 269 AN XY: 135888

Gnomad AFR exome AF: 0.0342

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00111 AC: 1619 AN: 1461872 Hom.: 17 Cov.: 31 AF XY: 0.000936 AC XY: 681 AN XY: 727240

Gnomad4 AFR exome AF: 0.0354

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00992 AC: 1510 AN: 152282 Hom.: 31 Cov.: 33 AF XY: 0.0100 AC XY: 748 AN XY: 74438

Gnomad4 AFR AF: 0.0341

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00228 Hom.: 13

Bravo AF: 0.0112

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	4.0
Dann	Benign	0.38

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

Other links and lift over

dbSNP: rs11568704; hg19: chr13-95686955;