NM_005845.5:c.3211-4381C>G

Variant names:

• chr13-95067240-G-C
• rs1189457
• NM_005845.5:c.3211-4381C>G

Variant summary

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

The NM_005845.5(ABCC4):​c.3211-4381C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,984 control chromosomes in the GnomAD database, including 25,958 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 0.58 (25958 hom., cov: 32)
• Consequence: ABCC4 NM_005845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	NM_005845.5	MANE Select	c.3211-4381C>G		intron	N/A	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.3070-4381C>G		intron	N/A	NP_001288758.1	O15439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3211-4381C>G		intron	N/A	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000967420.1		c.3211-4381C>G		intron	N/A	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.3208-4381C>G		intron	N/A	ENSP00000637480.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88366 AN: 151866 Hom.: 25960 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.614

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.582 AC: 88400 AN: 151984 Hom.: 25958 Cov.: 32 AF XY: 0.589 AC XY: 43777 AN XY: 74286

African (AFR) AF: 0.515 AC: 21350 AN: 41432

American (AMR) AF: 0.607 AC: 9269 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2136 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2619 AN: 5162

South Asian (SAS) AF: 0.740 AC: 3562 AN: 4816

European-Finnish (FIN) AF: 0.679 AC: 7185 AN: 10578

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40318 AN: 67948

Other (OTH) AF: 0.613 AC: 1290 AN: 2106

Alfa AF: 0.590 Hom.: 3338

Bravo AF: 0.570

Asia WGS AF: 0.614 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.031
DANN	Benign	0.37
PhyloP100		-1.7
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: rs1189457; hg19: chr13-95719494; COSMIC: COSV107485117; COSMIC: COSV107485117;