NM_005845.5:c.2214-65T>C

Variant names:

• chr13-95163281-A-G
• rs3765535
• NM_005845.5:c.2214-65T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005845.5(ABCC4):​c.2214-65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,147,516 control chromosomes in the GnomAD database, including 15,236 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 0.21 (4500 hom., cov: 32)
  • Exomes 𝑓: 0.13 (10736 hom.)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 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.2214-65T>C		intron	N/A	NP_005836.2
	ABCC4	NM_001301829.2		c.2073-65T>C		intron	N/A	NP_001288758.1
	ABCC4	NM_001105515.3		c.2214-65T>C		intron	N/A	NP_001098985.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2214-65T>C		intron	N/A	ENSP00000494609.1
	ABCC4	ENST00000629385.1	TSL:1	c.2214-65T>C		intron	N/A	ENSP00000487081.1
	ABCC4	ENST00000646439.1		c.2073-65T>C		intron	N/A	ENSP00000494751.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31182 AN: 152060 Hom.: 4482 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.131 AC: 130004 AN: 995340 Hom.: 10736 AF XY: 0.131 AC XY: 66614 AN XY: 509988

African (AFR) AF: 0.426 AC: 9493 AN: 22268

American (AMR) AF: 0.230 AC: 6968 AN: 30316

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 2609 AN: 20826

East Asian (EAS) AF: 0.288 AC: 10258 AN: 35642

South Asian (SAS) AF: 0.184 AC: 12303 AN: 66926

European-Finnish (FIN) AF: 0.132 AC: 6657 AN: 50368

Middle Eastern (MID) AF: 0.156 AC: 655 AN: 4192

European-Non Finnish (NFE) AF: 0.103 AC: 74415 AN: 720474

Other (OTH) AF: 0.150 AC: 6646 AN: 44328

GnomAD4 genome AF: 0.205 AC: 31257 AN: 152176 Hom.: 4500 Cov.: 32 AF XY: 0.205 AC XY: 15290 AN XY: 74420

African (AFR) AF: 0.403 AC: 16714 AN: 41494

American (AMR) AF: 0.200 AC: 3065 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3472

East Asian (EAS) AF: 0.273 AC: 1410 AN: 5174

South Asian (SAS) AF: 0.201 AC: 971 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1430 AN: 10602

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6770 AN: 68006

Other (OTH) AF: 0.201 AC: 424 AN: 2114

Alfa AF: 0.126 Hom.: 2816

Bravo AF: 0.220

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		0.055
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: rs3765535; hg19: chr13-95815535;