rs11568682

chr13-95301231-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC102724149 (HGNC:):

ACMG classification

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 GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.74+10C>T		intron_variant		ENST00000645237.2
LOC102724149	XR_429273.4	n.281G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.74+10C>T		intron_variant			NM_005845.5	P1

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

GnomAD3 exomes AF: 0.0185 AC: 3971 AN: 214578 Hom.: 74 AF XY: 0.0181 AC XY: 2134 AN XY: 118118

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

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.: 47 Cov.: 33 AF XY: 0.0170 AC XY: 1268 AN XY: 74404

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.: 22

Bravo AF: 0.0127

Asia WGS AF: 0.00261 AC: 9 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

Other links and lift over

dbSNP: rs11568682; hg19: chr13-95953485;