chr13-95206658-C-T

Variant names:

• chr13-95206658-C-T
• rs11568703
• NM_005845.5:c.1035G>A

Variant summary

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

The NM_005845.5(ABCC4):​c.1035G>A​(p.Val345Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,614,168 control chromosomes in the GnomAD database, including 31 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 0.0045 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (24 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 5 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=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.362 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.1035G>A	p.Val345Val	synonymous	Exon 8 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.1035G>A	p.Val345Val	synonymous	Exon 8 of 30	NP_001288758.1
	ABCC4	NM_001105515.3		c.1035G>A	p.Val345Val	synonymous	Exon 8 of 21	NP_001098985.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.1035G>A	p.Val345Val	synonymous	Exon 8 of 31	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.1035G>A	p.Val345Val	synonymous	Exon 8 of 21	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.1035G>A	p.Val345Val	synonymous	Exon 8 of 30	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152170 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00478

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00517 AC: 1300 AN: 251374 AF XY: 0.00556

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00306

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0147

Gnomad NFE exome AF: 0.00492

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00428 AC: 6254 AN: 1461880 Hom.: 24 Cov.: 32 AF XY: 0.00441 AC XY: 3207 AN XY: 727240

African (AFR) AF: 0.000777 AC: 26 AN: 33480

American (AMR) AF: 0.00313 AC: 140 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 322 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00460 AC: 397 AN: 86250

European-Finnish (FIN) AF: 0.0132 AC: 703 AN: 53420

Middle Eastern (MID) AF: 0.0140 AC: 81 AN: 5768

European-Non Finnish (NFE) AF: 0.00386 AC: 4296 AN: 1112006

Other (OTH) AF: 0.00475 AC: 287 AN: 60396

GnomAD4 genome AF: 0.00449 AC: 684 AN: 152288 Hom.: 7 Cov.: 32 AF XY: 0.00501 AC XY: 373 AN XY: 74456

African (AFR) AF: 0.000505 AC: 21 AN: 41552

American (AMR) AF: 0.00712 AC: 109 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4822

European-Finnish (FIN) AF: 0.0151 AC: 160 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00478 AC: 325 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00460 Hom.: 9

Bravo AF: 0.00334

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00567

EpiControl AF: 0.00415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.72
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=97/3	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: rs11568703; hg19: chr13-95858912;