rs11568655

Positions:

• chr13-95062760-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005845.5(ABCC4):​c.3310T>C​(p.Leu1104=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00502 in 1,614,030 control chromosomes in the GnomAD database, including 335 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 0.026 (188 hom., cov: 30)
  • Exomes 𝑓: 0.0029 (147 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.3310T>C	p.Leu1104=	synonymous_variant	26/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.3169T>C	p.Leu1057=	synonymous_variant	25/30
ABCC4	XM_047430034.1	c.3181T>C	p.Leu1061=	synonymous_variant	26/31
ABCC4	XM_047430035.1	c.2761T>C	p.Leu921=	synonymous_variant	23/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.3310T>C	p.Leu1104=	synonymous_variant	26/31		NM_005845.5	P1
ABCC4	ENST00000646439.1	c.3169T>C	p.Leu1057=	synonymous_variant	25/30
ABCC4	ENST00000643051.1	c.*935T>C		3_prime_UTR_variant, NMD_transcript_variant	27/33
ABCC4	ENST00000643842.1	c.*3356T>C		3_prime_UTR_variant, NMD_transcript_variant	27/32

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3924 AN: 152142 Hom.: 188 Cov.: 30

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00936

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00655 AC: 1647 AN: 251318 Hom.: 59 AF XY: 0.00487 AC XY: 661 AN XY: 135832

Gnomad AFR exome AF: 0.0863

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000519

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00285 AC: 4170 AN: 1461770 Hom.: 147 Cov.: 38 AF XY: 0.00250 AC XY: 1815 AN XY: 727176

Gnomad4 AFR exome AF: 0.0906

Gnomad4 AMR exome AF: 0.00534

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000449

Gnomad4 OTH exome AF: 0.00568

GnomAD4 genome AF: 0.0258 AC: 3931 AN: 152260 Hom.: 188 Cov.: 30 AF XY: 0.0258 AC XY: 1922 AN XY: 74456

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.00935

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00831 Hom.: 70

Bravo AF: 0.0287

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11568655; hg19: chr13-95715014;