chr13-95186749-G-A

Variant names:

• chr13-95186749-G-A
• rs1557070
• NM_005845.5:c.1497C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005845.5(ABCC4):​c.1497C>T​(p.Tyr499Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,700 control chromosomes in the GnomAD database, including 2,563 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 0.073 (1299 hom., cov: 33)
  • Exomes 𝑓: 0.0083 (1264 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 15 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.647 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.1497C>T	p.Tyr499Tyr	synonymous	Exon 11 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.1497C>T	p.Tyr499Tyr	synonymous	Exon 11 of 30	NP_001288758.1
	ABCC4	NM_001105515.3		c.1497C>T	p.Tyr499Tyr	synonymous	Exon 11 of 21	NP_001098985.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.1497C>T	p.Tyr499Tyr	synonymous	Exon 11 of 31	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.1497C>T	p.Tyr499Tyr	synonymous	Exon 11 of 21	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.1497C>T	p.Tyr499Tyr	synonymous	Exon 11 of 30	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11021 AN: 151886 Hom.: 1293 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.0548

GnomAD2 exomes AF: 0.0195 AC: 4906 AN: 251316 AF XY: 0.0144

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.00704

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00830 AC: 12136 AN: 1461696 Hom.: 1264 Cov.: 31 AF XY: 0.00716 AC XY: 5205 AN XY: 727166

African (AFR) AF: 0.261 AC: 8725 AN: 33460

American (AMR) AF: 0.0153 AC: 684 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00827 AC: 216 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00117 AC: 101 AN: 86238

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.0234 AC: 135 AN: 5768

European-Non Finnish (NFE) AF: 0.00102 AC: 1131 AN: 1111908

Other (OTH) AF: 0.0189 AC: 1143 AN: 60380

GnomAD4 genome AF: 0.0727 AC: 11055 AN: 152004 Hom.: 1299 Cov.: 33 AF XY: 0.0697 AC XY: 5182 AN XY: 74294

African (AFR) AF: 0.248 AC: 10286 AN: 41418

American (AMR) AF: 0.0310 AC: 473 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00952 AC: 33 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00176 AC: 120 AN: 68000

Other (OTH) AF: 0.0542 AC: 114 AN: 2104

Alfa AF: 0.0264 Hom.: 1558

Bravo AF: 0.0814

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.4
DANN	Benign	0.51
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs1557070; hg19: chr13-95839003;