rs11568702

Variant names:

• chr13-95206524-A-T
• rs11568702
• NM_005845.5:c.1161+8T>A

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.1161+8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,611,314 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (21 hom., cov: 32)
  • Exomes 𝑓: 0.016 (242 hom.)
• Consequence: ABCC4 NM_005845.5 splice_region, intron
• Scores: Splicing: ADA: 0.001266
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0126 (1914/152270) while in subpopulation NFE AF = 0.0207 (1408/68018). AF 95% confidence interval is 0.0198. There are 21 homozygotes in GnomAd4. There are 913 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.1161+8T>A		splice_region_variant, intron_variant	Intron 8 of 30	ENST00000645237.2	NP_005836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.1161+8T>A		splice_region_variant, intron_variant	Intron 8 of 30		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1914 AN: 152152 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.0126 AC: 3169 AN: 250776 AF XY: 0.0126

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.00507

Gnomad ASJ exome AF: 0.0164

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0224

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0118

GnomAD4 exome AF: 0.0160 AC: 23309 AN: 1459044 Hom.: 242 Cov.: 32 AF XY: 0.0159 AC XY: 11522 AN XY: 725186

Gnomad4 AFR exome AF: 0.00224 AC: 75 AN: 33434

Gnomad4 AMR exome AF: 0.00551 AC: 246 AN: 44678

Gnomad4 ASJ exome AF: 0.0167 AC: 435 AN: 26108

Gnomad4 EAS exome AF: 0.0000758 AC: 3 AN: 39596

Gnomad4 SAS exome AF: 0.00242 AC: 209 AN: 86214

Gnomad4 FIN exome AF: 0.0209 AC: 1114 AN: 53394

Gnomad4 NFE exome AF: 0.0184 AC: 20390 AN: 1109560

Gnomad4 Remaining exome AF: 0.0137 AC: 827 AN: 60306

GnomAD4 genome AF: 0.0126 AC: 1914 AN: 152270 Hom.: 21 Cov.: 32 AF XY: 0.0123 AC XY: 913 AN XY: 74440

Gnomad4 AFR AF: 0.00255 AC: 0.00254992 AN: 0.00254992

Gnomad4 AMR AF: 0.00504 AC: 0.00503729 AN: 0.00503729

Gnomad4 ASJ AF: 0.0130 AC: 0.0129833 AN: 0.0129833

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00125 AC: 0.00124533 AN: 0.00124533

Gnomad4 FIN AF: 0.0230 AC: 0.0229972 AN: 0.0229972

Gnomad4 NFE AF: 0.0207 AC: 0.0207004 AN: 0.0207004

Gnomad4 OTH AF: 0.00993 AC: 0.00993377 AN: 0.00993377

Alfa AF: 0.0194 Hom.: 14

Bravo AF: 0.0102

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0183

EpiControl AF: 0.0171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.79
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.016
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: rs11568702; hg19: chr13-95858778;