NM_005845.5:c.2847C>T

Variant names:

• chr13-95074284-G-A
• rs11568708
• NM_005845.5:c.2847C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005845.5(ABCC4):​c.2847C>T​(p.Ala949Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,613,804 control chromosomes in the GnomAD database, including 1 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 0.0031 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• Publications: 3 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.77 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.2847C>T	p.Ala949Ala	synonymous	Exon 23 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.2706C>T	p.Ala902Ala	synonymous	Exon 22 of 30	NP_001288758.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2847C>T	p.Ala949Ala	synonymous	Exon 23 of 31	ENSP00000494609.1
	ABCC4	ENST00000967420.1		c.2847C>T	p.Ala949Ala	synonymous	Exon 23 of 31	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.2844C>T	p.Ala948Ala	synonymous	Exon 23 of 31	ENSP00000637480.1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 464 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000794 AC: 199 AN: 250522 AF XY: 0.000532

Gnomad AFR exome AF: 0.0107

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000357 AC: 522 AN: 1461538 Hom.: 1 Cov.: 29 AF XY: 0.000286 AC XY: 208 AN XY: 727028

African (AFR) AF: 0.0128 AC: 427 AN: 33462

American (AMR) AF: 0.000649 AC: 29 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39674

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111878

Other (OTH) AF: 0.000696 AC: 42 AN: 60382

GnomAD4 genome AF: 0.00305 AC: 465 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.00277 AC XY: 206 AN XY: 74446

African (AFR) AF: 0.0109 AC: 451 AN: 41540

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00256 Hom.: 2

Bravo AF: 0.00368

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.7
DANN	Benign	0.48
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11568708; hg19: chr13-95726538;