chr13-95075526-T-C

Variant names:

• chr13-95075526-T-C
• rs1678339
• NM_005845.5:c.2712A>G

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.2712A>G​(p.Leu904Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 1,613,966 control chromosomes in the GnomAD database, including 722,004 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 0.92 (64301 hom., cov: 31)
  • Exomes 𝑓: 0.95 (657703 hom.)
• Consequence: ABCC4 NM_005845.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 30 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=-0.64).
• BP7: Synonymous conserved (PhyloP=-2.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 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.2712A>G	p.Leu904Leu	synonymous	Exon 22 of 31	NP_005836.2
	ABCC4	NM_001301829.2		c.2571A>G	p.Leu857Leu	synonymous	Exon 21 of 30	NP_001288758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.2712A>G	p.Leu904Leu	synonymous	Exon 22 of 31	ENSP00000494609.1
	ABCC4	ENST00000646439.1		c.2571A>G	p.Leu857Leu	synonymous	Exon 21 of 30	ENSP00000494751.1
	ABCC4	ENST00000467685.2	TSL:3	n.185A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139586 AN: 152040 Hom.: 64252 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.938

GnomAD2 exomes AF: 0.929 AC: 233219 AN: 251072 AF XY: 0.934

Gnomad AFR exome AF: 0.854

Gnomad AMR exome AF: 0.929

Gnomad ASJ exome AF: 0.958

Gnomad EAS exome AF: 0.796

Gnomad FIN exome AF: 0.914

Gnomad NFE exome AF: 0.954

Gnomad OTH exome AF: 0.937

GnomAD4 exome AF: 0.948 AC: 1385421 AN: 1461808 Hom.: 657703 Cov.: 57 AF XY: 0.948 AC XY: 689599 AN XY: 727212

African (AFR) AF: 0.850 AC: 28448 AN: 33474

American (AMR) AF: 0.931 AC: 41646 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 25031 AN: 26134

East Asian (EAS) AF: 0.764 AC: 30313 AN: 39694

South Asian (SAS) AF: 0.955 AC: 82331 AN: 86254

European-Finnish (FIN) AF: 0.915 AC: 48895 AN: 53416

Middle Eastern (MID) AF: 0.950 AC: 5479 AN: 5768

European-Non Finnish (NFE) AF: 0.959 AC: 1066547 AN: 1111952

Other (OTH) AF: 0.939 AC: 56731 AN: 60392

GnomAD4 genome AF: 0.918 AC: 139690 AN: 152158 Hom.: 64301 Cov.: 31 AF XY: 0.917 AC XY: 68234 AN XY: 74398

African (AFR) AF: 0.858 AC: 35620 AN: 41498

American (AMR) AF: 0.936 AC: 14300 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3338 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4085 AN: 5158

South Asian (SAS) AF: 0.945 AC: 4554 AN: 4818

European-Finnish (FIN) AF: 0.917 AC: 9718 AN: 10594

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64959 AN: 68016

Other (OTH) AF: 0.939 AC: 1985 AN: 2114

Alfa AF: 0.942 Hom.: 317792

Bravo AF: 0.916

Asia WGS AF: 0.869 AC: 3024 AN: 3476

EpiCase AF: 0.949

EpiControl AF: 0.954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.96
DANN	Benign	0.67
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs1678339; hg19: chr13-95727780; COSMIC: COSV65312135; COSMIC: COSV65312135;