chr13-95166191-G-A

Variant names:

• chr13-95166191-G-A
• rs11568698
• NM_005845.5:c.2001C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The ENST00000645237.2(ABCC4):​c.2001C>T​(p.Pro667Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,614,130 control chromosomes in the GnomAD database, including 3 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 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: ABCC4 ENST00000645237.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.217 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645237.2. 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.2001C>T	p.Pro667Pro	synonymous	Exon 15 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.2001C>T	p.Pro667Pro	synonymous	Exon 15 of 30	NP_001288758.1
	ABCC4	NM_001105515.3		c.2001C>T	p.Pro667Pro	synonymous	Exon 15 of 21	NP_001098985.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2001C>T	p.Pro667Pro	synonymous	Exon 15 of 31	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.2001C>T	p.Pro667Pro	synonymous	Exon 15 of 21	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.2001C>T	p.Pro667Pro	synonymous	Exon 15 of 30	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 297 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00673

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000625 AC: 157 AN: 251268 AF XY: 0.000420

Gnomad AFR exome AF: 0.00664

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000245 AC: 358 AN: 1461846 Hom.: 3 Cov.: 31 AF XY: 0.000199 AC XY: 145 AN XY: 727220

African (AFR) AF: 0.00699 AC: 234 AN: 33480

American (AMR) AF: 0.000648 AC: 29 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00153 AC: 40 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111980

Other (OTH) AF: 0.000580 AC: 35 AN: 60396

GnomAD4 genome AF: 0.00195 AC: 297 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.00191 AC XY: 142 AN XY: 74464

African (AFR) AF: 0.00671 AC: 279 AN: 41564

American (AMR) AF: 0.000523 AC: 8 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.0
DANN	Benign	0.60
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs11568698; hg19: chr13-95818445;