13-95062722-C-T

Variant names:

• chr13-95062722-C-T
• rs1751034
• NM_005845.5:c.3348G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005845.5(ABCC4):​c.3348G>A​(p.Lys1116Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,613,128 control chromosomes in the GnomAD database, including 540,650 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 0.79 (47774 hom., cov: 29)
  • Exomes 𝑓: 0.82 (492876 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 61 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=0.423 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

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.3348G>A	p.Lys1116Lys	synonymous	Exon 26 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.3207G>A	p.Lys1069Lys	synonymous	Exon 25 of 30	NP_001288758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3348G>A	p.Lys1116Lys	synonymous	Exon 26 of 31	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.3207G>A	p.Lys1069Lys	synonymous	Exon 25 of 30	ENSP00000494751.1
	ABCC4	ENST00000643051.1		n.*973G>A		non_coding_transcript_exon	Exon 27 of 33	ENSP00000495513.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120240 AN: 151768 Hom.: 47742 Cov.: 29

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.793

GnomAD2 exomes AF: 0.809 AC: 203115 AN: 251048 AF XY: 0.818

Gnomad AFR exome AF: 0.739

Gnomad AMR exome AF: 0.742

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.786

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.817

Gnomad OTH exome AF: 0.796

GnomAD4 exome AF: 0.820 AC: 1198678 AN: 1461242 Hom.: 492876 Cov.: 42 AF XY: 0.823 AC XY: 598591 AN XY: 726940

African (AFR) AF: 0.735 AC: 24598 AN: 33444

American (AMR) AF: 0.743 AC: 33223 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 19361 AN: 26120

East Asian (EAS) AF: 0.753 AC: 29896 AN: 39690

South Asian (SAS) AF: 0.905 AC: 77972 AN: 86170

European-Finnish (FIN) AF: 0.844 AC: 45095 AN: 53408

Middle Eastern (MID) AF: 0.776 AC: 4478 AN: 5768

European-Non Finnish (NFE) AF: 0.823 AC: 915190 AN: 1111596

Other (OTH) AF: 0.810 AC: 48865 AN: 60352

GnomAD4 genome AF: 0.792 AC: 120319 AN: 151886 Hom.: 47774 Cov.: 29 AF XY: 0.794 AC XY: 58939 AN XY: 74252

African (AFR) AF: 0.741 AC: 30653 AN: 41394

American (AMR) AF: 0.751 AC: 11452 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2575 AN: 3468

East Asian (EAS) AF: 0.785 AC: 4045 AN: 5152

South Asian (SAS) AF: 0.900 AC: 4337 AN: 4820

European-Finnish (FIN) AF: 0.847 AC: 8927 AN: 10540

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55763 AN: 67950

Other (OTH) AF: 0.794 AC: 1673 AN: 2106

Alfa AF: 0.805 Hom.: 147837

Bravo AF: 0.781

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	4.6
DANN	Benign	0.56
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1751034; hg19: chr13-95714976; COSMIC: COSV65309863;